NCT03577782

Brief Summary

HIV cannot be eliminated and remains in the body despite the treatment that is used for HIV-infection called antiretroviral treatment (ART). Individuals undergoing ART interruption rapidly experience virus rebound in the blood. The current alternative therapeutic strategies to antiretroviral treatment have the aim to achieve the elimination of the virus in blood in the absence of ART. New drugs associated to ART that allow the elimination of the virus in the blood after ART withdrawn are needed. In monkeys infected with SIV, the analog of HIV, the virus has disappeared from the blood after administration of a compound and cessation of ART. There is an equivalent compound in humans called Vedolizumab. The aim of the present study is to research if Vedolizumab combined with ART, in subjects without previous ART, is able to eliminate the virus from the blood after ART is not taken.

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
12

participants targeted

Target at below P25 for phase_1 hiv-infections

Timeline
Completed

Started Sep 2018

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

June 12, 2018

Completed
23 days until next milestone

First Posted

Study publicly available on registry

July 5, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2018

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2020

Completed
Last Updated

July 5, 2018

Status Verified

June 1, 2018

Enrollment Period

1.7 years

First QC Date

June 12, 2018

Last Update Submit

June 22, 2018

Conditions

HIV Infections

Keywords

HIVCD4+T-cellReservoirCureAntiretroviral therapyVedolizumabGutAlpha4Beta7gp120Interruption

Outcome Measures

Primary Outcomes (2)

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    The number of adverse events and severity during Vedolizumab infusions and during all the follow up.

    48 weeks

  • Plasma viral load rebound or remision after interrupting Vedolizumab infusions and ART

    Quantitative plasma viral load (Roche HIV-1 RNA Viral Load Assay) measured before and after interrupting Vedolizumab infusions and ART.

    48 weeks

Study Arms (1)

Single group

EXPERIMENTAL

HIV-infected subjects with no previous ART will begin ART together with Vedolizumab infusions at week 0, 4, 8, 12, 16, 20 and 24 weeks. At this time point ART and Vedolizumab treatment will be interrupted. Patients will be followed up until week 48. ART will be resumed if CD4+ T-cell levels drop below 350 CD4+/μL and/or viral load increase above 10e5 HIV-RNA copies/mL (two consecutive measurements).

Biological: Entyvio (Vedolizumab)

Interventions

Entyvio (Vedolizumab)BIOLOGICAL

1. Antiretroviral treatment consisting in Dolutegravir (Tivicay) (50mg) + Tenofovir alafenamide (TAF) (25mg) / Emtricitabina (FTC) (200mg) (Descovy), once daily during 24 weeks. 2. Entyvio (Vedolizumab) (300mg), 7 intravenous infusions at week 0 (baseline) (concomitant with ART onset), 4, 8, 12, 16, 20 and 24. At week 24 ART and Vedolizumab administration will be interrupted. ART will be resumed if CD4+ T-cell levels drop below 350 CD4+/μL and/or viral load increase above 10e5 HIV-RNA copies/mL (two consecutive measurements). Patients will be followed up until week 48.

Single group

Eligibility Criteria

Age18 Years - 65 Years
Sexall(Gender-based eligibility)
Gender Eligibility DetailsWomen during pregnancy or breast-feeding will be excluded. Women must agree to use suitable contraception method (hormonal or barrier method of birth control; abstinence) before entry and during the study.
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Individuals with documented HIV-infection. Aged, 18 - 65 years.
  • HIV-RNA \>1x10e4 copies/mL.
  • CD4+ T-cell counts \>350 cells//μL
  • To accept analytical ART interruption.

You may not qualify if:

  • Presence of major resistance mutations to the antiretrovirals used.
  • Active opportunistic infections.
  • Pregnancy or breastfeeding
  • Active hepatitis C or B virus infection.
  • Active or latent tuberculosis not treated.
  • Cirrhosis, portal hypertension and/or hypersplenism of any etiology.
  • Current or past neoplasia susceptible to be treated with steroids, immunotherapy or chemotherapy.
  • Abnormal laboratory measurements grade 3 or 4.
  • Concomitant use of drugs with pharmacological interactions with the treatment of the study based on the technical data sheet of the products.
  • Creatinine clearance \<50mL/min.
  • Any type of vaccination (e.g., hepatitis B virus, influenza…) two weeks before the beginning of the study.
  • Cardiovascular disease (e.g., acute coronary syndrome, heart failure…).
  • Neurological or neuro psychiatric disorder which symptoms may interfere with the safety and tolerability analysis.
  • Alcohol abuse and/or drugs that may interfere with the study treatment.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Virgen del Rocío University Hospital

Seville, 41013, Spain

RECRUITING

Related Publications (9)

  • Pernas M, Tarancon-Diez L, Rodriguez-Gallego E, Gomez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, Leon A, Rodriguez C, Benito JM, Rallon N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, Garcia F, Alcami J, Munoz-Fernandez M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. J Virol. 2018 Feb 12;92(5):e01805-17. doi: 10.1128/JVI.01805-17. Print 2018 Mar 1.

    PMID: 29212942BACKGROUND

  • 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: 19933330BACKGROUND

  • 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: 18264102BACKGROUND

  • Guzzo C, Ichikawa D, Park C, Phillips D, Liu Q, Zhang P, Kwon A, Miao H, Lu J, Rehm C, Arthos J, Cicala C, Cohen MS, Fauci AS, Kehrl JH, Lusso P. Virion incorporation of integrin alpha4beta7 facilitates HIV-1 infection and intestinal homing. Sci Immunol. 2017 May 12;2(11):eaam7341. doi: 10.1126/sciimmunol.aam7341.

    PMID: 28763793BACKGROUND

  • 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: 25419708BACKGROUND

  • Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, Sidell N, Kane MA, Yu J, Jones JW, Santangelo PJ, Zurla C, McKinnon LR, Arnold KB, Woody CE, Walter L, Roos C, Noll A, Van Ryk D, Jelicic K, Cimbro R, Gumber S, Reid MD, Adsay V, Amancha PK, Mayne AE, Parslow TG, Fauci AS, Ansari AA. Sustained virologic control in SIV+ macaques after antiretroviral and alpha4beta7 antibody therapy. Science. 2016 Oct 14;354(6309):197-202. doi: 10.1126/science.aag1276.

    PMID: 27738167BACKGROUND

  • Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.

    PMID: 23964932BACKGROUND

  • Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.

    PMID: 23964933BACKGROUND

  • Jimenez-Leon MR, Gasca-Capote C, Roca-Oporto C, Espinosa N, Sobrino S, Fontillon-Alberdi M, Gao C, Roseto I, Gladkov G, Rivas-Jeremias I, Neukam K, Sanchez-Hernandez JG, Rigo-Bonnin R, Cervera-Barajas AJ, Mesones R, Garcia F, Alvarez-Rios AI, Bachiller S, Vitalle J, Perez-Gomez A, Camacho-Sojo MI, Gallego I, Brander C, McGowan I, Mothe B, Viciana P, Yu X, Lichterfeld M, Lopez-Cortes LF, Ruiz-Mateos E. Vedolizumab and ART in recent HIV-1 infection unveil the role of alpha4beta7 in reservoir size. JCI Insight. 2024 Jul 9;9(16):e182312. doi: 10.1172/jci.insight.182312.

    PMID: 38980725DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

  • Ezequiel Ruiz-Mateos, PhD

    Virgen del Rocio University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ezequiel Ruiz-Mateos, PhD

CONTACT

+34955923109ezequiel.ruizmateos@gmail.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: HIV-infected subjects with no previous ART will begin ART together with Vedolizumab infusions at week 0, 4, 8, 12, 16, 20 and 24 weeks. At this time point ART and Vedolizumab treatment will be interrupted. Patients will be followed up until week 48. ART will be resumed if CD4+ T-cell levels drop below 350 CD4+/μL and/or viral load increases above 10e5 HIV-RNA copies/mL (two consecutive measurements).
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Researcher Andalusian Health System

Study Record Dates

First Submitted

June 12, 2018

First Posted

July 5, 2018

Study Start

September 1, 2018

Primary Completion

May 1, 2020

Study Completion

May 1, 2020

Last Updated

July 5, 2018

Record last verified: 2018-06

Locations

ES(1)