AzTrials
AzTrials

Chronic Obstructive Pulmonary DiseasePhase 2EVOLUTIONNCT01541852

Losmapimod in Chronic Obstructive Pulmonary Disease Patients Stratified by Fibrinogen.

A Phase 2 study testing Losmapimod in people with Chronic Obstructive Pulmonary Disease, run by Cambridge University Hospitals NHS Foundation Trust at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The main purpose of this study is to determine the effect of Losmapimod on blood vessels in patients with Chronic Obstructive Pulmonary Disease (COPD). Although COPD is a lung disease, it is also associated with an increased risk of cardiovascular disease (e.g. heart attacks and stroke). Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Chronic Obstructive Pulmonary Disease
What is being tested?
Losmapimod
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
72 participants
Where
2 sitesUnited Kingdom
Study dates
Jun 2012to Feb 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients between 50 and 85 years of age inclusive at screening, with a body weight ≥ 45 kg and BMI ≤35 kg/m2.
  • Patients with a clinical diagnosis of COPD with GOLD Stages 1, 2, 3 or 4, or GOLD-U.
  • Patient has FEV1/FVC < 0.7 post-bronchodilator.
  • 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).
  • Baseline fibrinogen value of >2.8 g/L (Klauss method)
  • 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%).
  • 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.
  • Patients who fulfil local imaging centre requirements will be enrolled.

Who cannot join

  • The presence of any of the following will preclude patient inclusion:
  • Inability in the opinion of the PI to provide Informed Consent.
  • A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, carotid endarterectomy).
  • Patients on daunorubicin, doxorubicin, topotecan, mitoxantrone.
  • Previous lung reduction surgery.
  • 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.
Show all 21Show fewer
  • A positive pre-trial Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Patients with known chronic infections such as HIV or known active tuberculosis.
  • Patients with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).
  • Insulin controlled Type 1 or Type 2 diabetics.
  • Diabetics on oral hypoglycaemics/diet with 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]
  • 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)
  • History of malignancy within the past 5 years (with the exception of localized carcinoma of the skin that has been resected for cure).
  • Previous exposure to Losmapimod.
  • Patients who have donated more than 500 mL of blood within 2 months prior to the trial medication administration, Visit 3 (Day 1).
  • 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).
  • History of alcohol/drug abuse or dependence within 6 months of the trial, Screening Visit 1 (Day -45 to -14).
  • Women of childbearing potential are excluded from this trial.
  • 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.
  • Use of systemic corticosteroids (oral or IV) 4 weeks prior to Visit 2 (Day -14 to -1).

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, Cambridgeshire, CB2 0QQ

  • Royal Brompton & Harefield NHS Foundation Trust

    London, London, SW3 6NP

Other trials in United Kingdom

About this study

Official title: An Evaluation Of Losmapimod in Patients With Chronic Obstructive Pulmonary Disease (COPD) With Systemic Inflammation Stratified Using Fibrinogen (EVOLUTION)

The main purpose of this study is to determine the effect of Losmapimod on blood vessels in patients with Chronic Obstructive Pulmonary Disease (COPD). Although COPD is a lung disease, it is also associated with an increased risk of cardiovascular disease (e.g. heart attacks and stroke). The investigators believe that this is a result of inflammation within the body, which damages the lining (endothelium) and walls of blood vessels. These changes can promote the development of fatty deposits within the walls of arteries (atherosclerosis) which can rupture and block arteries causing damage.

Read the detailed description

The study aims to enrol sufficient COPD subjects (stratified by fibrinogen level) so that 60 patients complete the study. Study patients will have a 50% chance of receiving either Losmapimod or Placebo. Patients will be expected to attend for up to 12 visits, over a 24 week period. The visits consist of an initial screening visit, and 2 pre-dose imaging visits to include a PET-CT scan and an optional MRI scan. The next 7 visits (at 2-4 weekly intervals) involve blood tests and safety evaluations. A number of procedures including heart tracings (ECGs), non-invasive vascular measurements and lung function tests at the start and at the end of the study. Repeat imaging with PET-CT and MRI will be performed at the end of the study and a follow-up visit.

The purpose of the study is to see if the study medication has a beneficial effect on vascular function and structure. It is envisaged that this trial will help define more evolutionary biomarkers to focus on to help COPD patients in the future.

Being tested
Losmapimod, Placebo
Keywords
Vascular Inflammation, FDG PET-CT, COPD, Atherosclerosis, p38 MAP kinase inhibitor
Medical subject headings
Pulmonary Disease, Chronic Obstructive, Atherosclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LosmapimodDrug

    Also called GW856553

    One tablet of Losmapimod 7.5mg twice daily

  • PlaceboDrug

    Also called Lactose Monohydrate

    One tablet twice daily

Study groups in NCT01541852
Study groupRoleWhat they receive
LosmapimodActive comparator7.5mg tablet twice daily
Receives: Drug: Losmapimod
PlaceboPlacebo comparatorOne tablet twice daily
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Vascular inflammation on FDG PET-CT

    To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in Vascular inflammation as measured by FDG PET-CT

    Measured: Days 0 to Day 112

  2. Endothelial function as measured by flow mediated dilatation

    To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in endothelial function as measured by flow mediated dilatation

    Measured: Days 0 to Day 112

  3. Arterial structure and plaque characteristics on MRI

    To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in arterial structure and plaque characteristics as measured by MRI (MRI is an optional sub-study and analysis will be based on a sufficient number of datasets).

    Measured: Days 0 to Day 112

Secondary outcomes (7)

  1. Lung inflammation on FDG PET-CT

    To determine the effects of Losmapimod on the change in inflammation in lung tissue as assessed by FDG PET-CT

    Measured: Days 0 to 112

  2. Fat inflammation on FDG PET-CT

    To determine the effects of Losmapimod on the change in fat inflammation as assessed by FDG PET-CT

    Measured: Days 0 to 112

  3. Arterial stiffness as measured by arterial tonometry

    To determine the effects of Losmapimod on the change in arterial stiffness as measured by arterial tonometry

    Measured: Days 0 to 112

  4. Blood biomarkers of systemic inflammation (Fibrinogen and high sensitivity CRP)

    To determine the effects of Losmapimod on the change in blood biomarkers of inflammation such as Fibrinogen and high sensitivity CRP

    Measured: Days 0 to 112

  5. Indices of lung function (6 minute walk test and sniff nasal inspiratory pressure)

    To determine the effects of Losmapimod on the change in indices of lung function and physical performance as measured by 6 minute walk test and sniff nasal inspiratory pressure

    Measured: Days 0 to 112

  6. Body composition and fat as assessed by Free fat mass index

    To determine the effects of Losmapimod on the change in body composition and fat as measured by Free fat mass index

    Measured: Days 0 to 112

  7. Number of adverse events as a measure of safety and tolerability

    To determine the effects of Losmapimod on the number of adverse events as a measure of safety and tolerability

    Measured: Days 0 to 112

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01541852
Sponsor's protocol ID
A092519
Other IDs
2011-004936-75
Acronym
EVOLUTION
Status last verified
Mar 2015
First submitted
20 Feb 2012
Last updated
17 Mar 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Losmapimod in people with Chronic Obstructive Pulmonary Disease, run by Cambridge University Hospitals NHS Foundation Trust at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Vascular inflammation on FDG PET-CT (time frame: Days 0 to Day 112). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01541852.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2015; AzTrials last refreshed its copy on 7 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in