E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epstein-Barr virus infection in patients with chronic obstructive pulmonary disease. |
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E.1.1.1 | Medical condition in easily understood language |
Epstein-Barr virus infection in patients with chronic obstructive pulmonary disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this study is to evaluate the safety of valaciclovir in the suppression of Epstein-Barr virus (EBV) in patients with chronic obstructive pulmonary disease (COPD).
The study objective is to undertake a randomised double-blind, placebo-controlled (i.e. dummy medication) clinical trial to study whether valaciclovir is safe in patients with COPD and improves important clinical outcomes. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to investigate if valaciclovir has an effect on important clinical parameters (clinical symptoms and lung function) and surrogate markers of biological outcomes in COPD. This will help in the future design of other clinical trials with valaciclovir or with other potential therapeutic agents.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
EViSCO Exploratory Bronchoscopy Sub-study (Version 1.0, 09/05/18)
Trial participants will be recruited to an exploratory sub-study on a voluntary basis and will indicate their consent to have a bronchoscopy at baseline and following 8 weeks treatment during the initial study visit. Participants undergoing bronchoscopy will have tissue specimens taken via bronchial biopsies and brushings. This will allow pathological assessment of the airway epithelium before and after treatment.
The bronchoscopy sub-study outcomes will be exploratory in nature and are listed below.
• Measurement of epithelial ICAM-1.
• Bronchial washings for measurement of airway inflammatory markers.
• Bronchial biopsy histology and immunohistopathology.
• Indices of nucleic acid expression including viral and genomic DNA, viral RNA, microRNA and mRNA analysis & methylation analysis.
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E.3 | Principal inclusion criteria |
1. Age over 18 years.
2. 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.
3. Presence of Epstein-Barr virus on sputum PCR analysis.
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E.4 | Principal exclusion criteria |
1. Respiratory failure (defined as long-term oxygen therapy).
2. 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).
3. A diagnosis of asthma.
4. Patients with known hypersensitivity to valaciclovir or aciclovir.
5. Patients unable to swallow study drug capsules.
6. Established diffuse interstitial lung disease (e.g. Idiopathic Pulmonary Fibrosis).
7. Established diagnosis of symptomatic bronchiectasis.
8. Patients known to be pregnant or breastfeeding.
9. Patients with an estimated creatinine clearance less than 50ml/minute.
10. Known participation in investigational medicinal product trials within 30 days.
11. Patients who do not adequately understand verbal or written information.
12. Concomitant use of nephrotoxic medicinal products or medicines associated with altered renal tubular secretion. Theseinlcude aminoglycosides, organoplatinum compounds, methotrexate, pentamidine, foscarnet, ciclosporin, tacrolimus,tenofovir, cimetidine and probenecid. As iodinated contrast used in radiological examinations can be nephrotoxicany patients with planned radiological contrast studies will be deferred for a reasonable time until after their contrast.
13. For the exploratory bronchoscopy sub-tudy 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).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study will be to evaluate the safety of valaciclovir one gram (three times daily for 8 weeks) for the suppression of Epstein-Barr virus in patients with COPD as defined by the incidence of serious adverse reactions (SARs). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Participants will be followed up for 4 weeks following completion of the 8 week treatment (i.e. follow up until week 12). |
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E.5.2 | Secondary end point(s) |
Clinical symptoms
Lung function (FEV1)
EBV quantitative PCR |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will end when 88 participants have been recruited and completed 12 week follow-up, samples analysed and database locked. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |