NCT01633476

Brief Summary

The purpose of this study is to determine whether Cytomegalovirus (CMV) reactivation in ANCA-associated vasculitis (AAV) patients can be effectively and safely reduced using an antiviral agent (valaciclovir) and whether this in turn improves the function of the immune system thereby also improving the body's ability to fight other infections. The primary hypothesis is that repeated episodes of CMV reactivation in AAV patients drive the expansion and functional impairment of CMV-specific T-cells, with increased susceptibility to infection. Inhibition of CMV replication with valaciclovir will block further stimulation of CMV specific T-cells and increase the functional capacity of the immune system.

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
38

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jul 2013

Typical duration 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

June 29, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 4, 2012

Completed
12 months until next milestone

Study Start

First participant enrolled

July 1, 2013

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2017

Completed
Last Updated

November 30, 2016

Status Verified

November 1, 2016

Enrollment Period

2.6 years

First QC Date

June 29, 2012

Last Update Submit

November 29, 2016

Conditions

ANCA Associated VasculitisCMV Infection

Keywords

CMVANCA associated vasculitisCD4+CD28- T-cellsValaciclovir

Outcome Measures

Primary Outcomes (1)

  • Proportion of patients with CMV reactivation and time to CMV reactivation

    As assessed by measurable viral load on quantitative blood and urine CMV PCR.

    Over 12 month period

Secondary Outcomes (4)

  • Proportion of patients experiencing adverse events sufficient to stop treatment

    Over 6 month period (treatment period)

  • Change in the proportion of the CD4+ CMV specific T cell population from baseline to 6 months

    Baseline to 6 months

  • Change in markers of inflammation from baseline to 6 months

    Baseline to 6 months

  • Persistence of valaciclovir effect on proportion of CD4+ CMV-specific T cells at 6 months post treatment (i.e. change from 6 months to 12 months)

    6 months to 12 months

Other Outcomes (2)

  • Change in the immune phenotype of the CD4+ and CD8+ T-cell compartment from baseline to 6 months

    Baseline to 6 months

  • Change in the immune phenotype of CD4+ CMV-specific T-cells

    Baseline to 6 months

Study Arms (2)

Valaciclovir

ACTIVE COMPARATOR

Active treatment with valaciclovir

Drug: Valaciclovir

No additional treatment

NO INTERVENTION

No additional treatment

Interventions

ValaciclovirDRUG

2g q.d.s. orally for 6 months (dose adjusted according to renal function)

Also known as: Brand names: Valtrex, Zelitrex
Valaciclovir

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Documented diagnosis of Wegener's granulomatosis (now called Granulomatosis with Polyangiitis), microscopic polyangiitis or renal limited vasculitis according to Chapel Hill Consensus Conference criteria.
  • In stable remission (no documented clinical disease activity) for at least 6 months prior to entry.
  • On maintenance immunosuppression with prednisolone, mycophenolate mofetil or azathioprine alone or in combination (maximum 2 agents).
  • Documented evidence of CMV infection (CMV-specific immunoglobulin G detected in peripheral blood).
  • Documentation that female patients of child bearing potential are not pregnant and using an appropriate form of contraception.
  • Written informed consent for study participation

You may not qualify if:

  • Stage 5 chronic kidney disease (eGFR\<15ml/minute/1.73m2).
  • Other significant chronic infection (HIV, HBV, HCV, TB).
  • B-cell or T-cell depleting therapy within 12 months.
  • Treatment with anti-CMV therapies in last month
  • Underlying medical conditions, which in the opinion of the Investigator place the patient at unacceptably high risk for participating in the study.
  • Inability to fully or appropriately participate in the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Wellcome Trust Clinical Research Facility

Birmingham, B15 2TH, United Kingdom

Location

Related Publications (4)

  • Morgan MD, Pachnio A, Begum J, Roberts D, Rasmussen N, Neil DA, Bajema I, Savage CO, Moss PA, Harper L. CD4+CD28- T cell expansion in granulomatosis with polyangiitis (Wegener's) is driven by latent cytomegalovirus infection and is associated with an increased risk of infection and mortality. Arthritis Rheum. 2011 Jul;63(7):2127-37. doi: 10.1002/art.30366.

    PMID: 21437878BACKGROUND

  • Chanouzas D, Sagmeister M, Faustini S, Nightingale P, Richter A, Ferro CJ, Morgan MD, Moss P, Harper L. Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. J Infect Dis. 2019 Jan 7;219(2):234-244. doi: 10.1093/infdis/jiy493.

    PMID: 30102389DERIVED

  • Chanouzas D, Dyall L, Nightingale P, Ferro C, Moss P, Morgan MD, Harper L. Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS): study protocol for a randomised controlled trial. Trials. 2016 Jul 22;17(1):338. doi: 10.1186/s13063-016-1482-2.

    PMID: 27450392DERIVED

  • Chanouzas D, Dyall L, Dale J, Moss P, Morgan M, Harper L. CD4+CD28- T-cell expansions in ANCA-associated vasculitis and association with arterial stiffness: baseline data from a randomised controlled trial. Lancet. 2015 Feb 26;385 Suppl 1:S30. doi: 10.1016/S0140-6736(15)60345-2.

    PMID: 26312852DERIVED

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisCytomegalovirus Infections

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Systemic VasculitisVasculitisVascular DiseasesCardiovascular DiseasesSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfections

Intervention Hierarchy (Ancestors)

AcyclovirGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Lorraine Harper, MRCP PhD

    University of Birmingham

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Nephrology

Study Record Dates

First Submitted

June 29, 2012

First Posted

July 4, 2012

Study Start

July 1, 2013

Primary Completion

February 1, 2016

Study Completion

September 1, 2017

Last Updated

November 30, 2016

Record last verified: 2016-11

Locations

GB(1)