Epstein-Barr Virus Suppression in Chronic Obstructive Pulmonary Disease (EViSCO): a Phase 2 Randomised Control Trial

NCT03699904 | Terminated Phase 2 DMC

• 1 other identifier: 14143JK-AS
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

COPD is a major public health problem and will shortly become the third most common cause of global mortality. There are currently no treatments that can meaningfully alter the progression of COPD or the time to death. Consequently novel therapeutic strategies for COPD are urgently required. This will be a randomised, double-blind, placebo-controlled, trial of Epstein-Barr virus suppression in COPD. Participants will be randomised to receive valaciclovir 1 gram three times daily for 8 weeks or matching placebo. The study will measure EBV suppression using quantitative PCR. Secondary outcomes will include Lung function quality of life and drug tolerability. The exploratory analysis will evaluate biomarkers of airway inflammation within the sputum and blood.

Conditions

COPD; EBV

Keywords

COPD; EBV

Outcome Measures

Primary Outcomes (2)

• Incidence of Serious Adverse Reactions (SARs)

  The primary outcome measure will be drug safety of valaciclovir (1 gram three times daily for 8 weeks) as defined by the incidence of Serious Adverse Reactions (SARs).

  Up to 28 days after completion of the study drug

• EBV viral load

  The primary efficacy outcome is suppression of Epstein-Barr virus in the sputum measured using quantitative PCR at baseline and 8 weeks.

  Change from baseline to 8 weeks.

Secondary Outcomes (2)

• Forced expiratory volume in 1 second (FEV1)

  Change from baseline to 8 weeks

• Drug tolerability as measured by the proportion of tablets self-administered.

  8 weeks

Other Outcomes (2)

• COPD assessment test (CAT) score

  Change from baseline to 8 weeks

• EQ-5D-5L health status questionnaire

  Change from baseline to 8 weeks

Study Arms (2)

Active arm

EXPERIMENTAL

Valaciclovir 1 gram orally three times daily for 8 weeks.

Drug: Valaciclovir

Placebo arm

PLACEBO COMPARATOR

Matching placebo capsules (containing Avicel blend). Two capsules three times daily for 8 weeks.

Drug: Placebo capsules (containing Avicel blend)

Interventions

Valaciclovir DRUG

Participants will self-administer Valaciclovir 1 gram three times daily for 8 weeks.

Active arm

Placebo capsules (containing Avicel blend) DRUG

Participants will self-administer two matching placebo capsules (containing Avicel blend) three times daily for 8 weeks.

Placebo arm

Eligibility Criteria

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

You may qualify if:

• Age over 18 years.
• Clinical diagnosis of COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease criteria (FEV1/FVC \<70%) with GOLD 2 and GOLD 3 airflow obstruction (FEV1 30-80% predicted) with significant symptoms.
• Presence of Epstein-Barr virus on sputum PCR analysis.

You may not qualify if:

• Respiratory failure (defined as long-term oxygen therapy).
• An acute exacerbation of COPD in the previous month (defined as an acute, sustained worsening of symptoms that is beyond normal day-to-day variations).
• A diagnosis of asthma.
• Patients with known hypersensitivity to valaciclovir or aciclovir.
• Patients unable to swallow study drug capsules.
• Established diffuse interstitial lung disease (e.g. Idiopathic Pulmonary Fibrosis).
• Established diagnosis of symptomatic bronchiectasis.
• Patients known to be pregnant or breastfeeding.
• Patients with an estimated creatinine clearance less than 50ml/minute.
• Known participation in investigational medicinal product trials within 30 days.
• Patients who do not adequately understand verbal or written information.
• Concomitant use of nephrotoxic medicinal products or medicines associated with altered renal tubular secretion. These include aminoglycosides, organoplatinum compounds, methotrexate, pentamidine, foscarnet, ciclosporin, tacrolimus,tenofovir, cimetidine and probenecid. As iodinated contrast used in radiological examinations can be nephrotoxicity patients with planned radiological contrast studies will be deferred for a reasonable time until after their contrast.
• For the exploratory bronchoscopy sub-study patients will require adequate oxygen saturations, FEV1 \>0.5 L and will not be performed while patients are taking aspirin or clopidogrel (BTS guidelines 2013).

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead
• Northern Ireland Clinical Trials Unit: collaborator
• Queen's University, Belfast: collaborator

Study Sites (1)

Belfast Health and Social Care Trust

Belfast, Down, BT5 7GX, United Kingdom

Location

Related Publications (1)

• Linden DA, Guo-Parke H, McKelvey MC, Einarsson GG, Lee AJ, Fairley DJ, Brown V, Lundy G, Campbell C, Logan D, McFarland M, Singh D, McAuley DF, Taggart CC, Kidney JC. Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial. Chest. 2023 Sep;164(3):625-636. doi: 10.1016/j.chest.2023.03.040. Epub 2023 Apr 1.

  PMID: 37011709 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Joe Kidney, MB, MD

  Belfast Health and Social Care Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be randomised, double-blind trial with matching placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel assignment.

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 9, 2018
• Study Start: October 11, 2018
• Primary Completion: May 7, 2020
• Study Completion: July 1, 2020
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

GB (1)