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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2011-004936-75
    Sponsor's Protocol Code Number:EVOLUTION
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-05-15
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2011-004936-75
    A.3Full title of the trial
    An Evaluation of Losmapimod in patients with Chronic Obstructive Pulmonary Disease (COPD) with systemic inflammation stratified using fibrinogen (EVOLUTION)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluating whether Losmapimod reduces inflammation in COPD patients.
    A.3.2Name or abbreviated title of the trial where available
    Losmapimod in COPD patients stratified by fibrinogen (EVOLUTION)
    A.4.1Sponsor's protocol code numberEVOLUTION
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01541852
    A.5.4Other Identifiers
    Name:R&D NumberNumber:A092519
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCambridge University Hospitals NHS Foundation Trust and University of Cambridge
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCambridge Clinical Trials Unit
    B.5.2Functional name of contact pointCarrie Bayliss
    B.5.3 Address:
    B.5.3.1Street AddressCambridge University Hospitals NHS Foundation Trust, Clinical School, Level 3 - Box 111
    B.5.3.2Town/ cityHills Road, Cambridge
    B.5.3.3Post codeCB2 0QQ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01223348158
    B.5.5Fax number01223 596471
    B.5.6E-mailcctu@addenbrookes.nhs.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameLosmapimod
    D.3.2Product code GW856553
    D.3.4Pharmaceutical form Coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLosmapimod
    D.3.9.3Other descriptive nameGW856553
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number7.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCoated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    The trial team will be looking at patients with Chronic Obstructive Pulmonary Disease and how inflammation affects them.
    E.1.1.1Medical condition in easily understood language
    Chronic Obstructive Pulmonary Disease
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10009033
    E.1.2Term Chronic obstructive pulmonary disease
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by 1. Vascular inflammation 2. Endothelial function 3. Arterial structure and plaque characteristics
    E.2.2Secondary objectives of the trial
    To determine the effects of Losmapimod on 1. Inflammation in lung tissue 2. Inflammation in fat 3. Arterial stiffness 4. Blood biomarkers of inflammation 5. Indices of lung function and physical performance 6. Body composition and fat 7. Safety and tolerability
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female patients between 50 and 85 years of age inclusive at screening, with a body weight ≥ 45 kg and BMI between 18 and 35 kg/m2 2. Patients with a clinical diagnosis of COPD with GOLD Stages 2, 3 or 4. 3. Patient has FEV1/FVC < 0.7 post-bronchodilator AND patient has FEV1 < 80% post dilator 4. Patient is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent) 5. Baseline fibrinogen value of ≥4.0g/L (Klauss method) 6. ALT < 2xULN at screening; alkaline phosphatase and bilirubin ≤ 1.5xULN at screening (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) 7. Patients must have a QTc <450 msec on screening (V1) ECG (using average value of triplicate ECGs). For patients with complete Right bundle branch block, the QTc must be <480msec on Screening V1 ECG. Patients with other ECG findings will be excluded if warranted at the discretion of the CI/PI. QTc readings will be QTcF and machine- read 8. (For the optional MRI sub-study): Patients who fulfil local imaging centre requirements will be enrolled
    E.4Principal exclusion criteria
    1. Inability to give Informed Consent. 2. A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, carotid endarterectomy). 3. Patients on daunorubicin, doxorubicin, topotecan, mitoxantrone. 4. Previous lung reduction surgery. 5. Patients with known clinically significant pulmonary diagnoses in which inflammation is thought to play a role including diagnosis of bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung disease, or α1-antitrypsin deficiency. 6. A positive pre-trial Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 7. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 8. Patients with known chronic infections such as HIV or known active tuberculosis. 9. Patients with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease). 10. Insulin controlled Type 1 or Type 2 diabetics. 11. Diabetics on oral hypoglycaemics/diet with fasting glucose > 7mmol/L OR HbA1c (DCCT) > 8% OR HbA1c (IFCC) > 64 mmol/mol, at screening. [note: fasting glucose to be checked again at first FDG-PET/CT scan, and if glucose > 11mmol/L at that visit, patients will be excluded from trial] 12. Participation in a previous research trial in the last 3 years which involved exposure to significant ionising radiation (i.e. cumulative research radiation dose >5 mSv) 13. History of malignancy within the past 5 years (with the exception of localized carcinoma of the skin that has been resected for cure). 14. Previous exposure to Losmapimod. 15. Patients who have donated more than 500 mL of blood within 2 months prior to the trial medication administration, Visit 3 (Day 1). 16. Participation in a clinical trial where the patient has received a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of the drug (whichever is longer) prior to the first dose of trial medication, Visit 3 (Day 1). 17. History of alcohol/drug abuse or dependence within 6 months of the trial, Screening Visit 1 (Day -45 to -14). 18. Women of childbearing potential are excluded from this trial. Women must be of non-childbearing potential [i.e. either postmenopausal or documented hysterectomy and/or bilateral oophorectomy – tubal ligation is not sufficient]. For the purposes of this trial, postmenopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. An unwillingness of male patients to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the patient to use a condom/spermicide in addition to having their female partner use another form of contraception such as an intrauterine device (IUD), diaphragm with spermicide, injectable progesterone, sub-dermal implants or a tubal ligation. 19. Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern. 20. Use of systemic corticosteroids (oral or IV) 4 weeks prior to Visit 3 (Day 1).
    E.5 End points
    E.5.1Primary end point(s)
    Change in vascular inflammation (using derivatives of Standard uptake value (SUV) and Tissue to background ratio (TBR) in the carotid and aortic arteries of subjects following 16 weeks of treatment. Change in flow mediated dilatation following 16 weeks treatment. Change in atheromatous plaque and vessel wall characteristic using MRI and/or FDG-PET/CT, following 16 weeks of treatment.
    E.5.2Secondary end point(s)
    Change in lung inflammation assessed by FDG-PET/CT, following 16 weeks of treatment. Change in visceral and subcutaneous fat inflammation and serum/plasma measures of systemic inflammation, following 16 weeks of treatment. Change in arterial stiffness measures (aortic pulse wave velocity and augmentation index), following 16 weeks of treatment. Change in baseline- corrected blood concentration of biomarkers. Change in spirometry (FEV1, FVC, FEV1/FVC ratio) and maximal SNIP and 6MWT following 16 weeks of treatment. Change in body composition as measured by BMI and FFMI, following a 16 week treatment. Safety and tolerability parameters, including physical examination, blood pressure, heart rate, 12-lead electrocardiogram (ECGs) recordings, clinical laboratory tests, lung function, and adverse event reporting
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    The end of trial definition will be 3 months after last patient last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days29
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    F.4.2.2In the whole clinical trial 0
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    There are no arrangements for participants to receive Losmapimod once the trial has finished. Losmapimod is in early phase trials and is therefore not available to participants at study end. Participants will receive normal standard of care.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-04-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-05-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-08-06
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