Crohn's Disease Clinical Trial
What is this clinical trial?
This study is designed to explore how effective, how safe and how tolerable different doses of a new drug, called laquinimod, is in patients who have Crohn's Disease.
Why is this clinical trial taking place?
As you may know, there are a variety of current medications available to treat Crohn's Disease. However, even though these may be effective, in some patients these medications can cause unpleasant side effects which are difficult to live with.
Current medications range from corticosteroids to intravenous drugs. These can work well to treat symptoms but some patients experience unwanted side effects. With the injectable drugs there is the inconvenience of injecting regularly, or having to come into the hospital for an infusion.
To this end, medical researchers are conducting clinical research trials in an effort to help develop new treatments, that work well but with less side effects.
This is one of these studies, where a new oral drug, which are medications taken by mouth, will be investigated to see if it is effective in treating the symptoms of Crohn's Disease and at the same time, having few side effects.
What type of clinical trial is this study?
This study is a Phase II clinical trial. This study is comparing the effect of daily treatment of laquinimod at four different doses of 0.5mg, 1mg, 1.5mg and 2mg compared to placebo (dummy drug), in people with Crohn's Disease. Each dose will be tested in four separate groups of approximately 45 participants starting at 0.5 mg dose which will be compared to placebo. The four groups will not receive a dose at the same time. The results of the 0.5mg dose group will be analysed statistically and by an independent committee made up of clinical experts who are not involved in the trial. If this dose appears safe, the next group will be given 1mg or placebo and the safety review process will be repeated before the next dose of 1.5mg or placebo is given. Each patient who agrees to participate will only receive one of the doses. You will be told which dose group you are in but not whether or not you will be receiving laquinimod or an inactive placebo.
In total, approximately 200 patients from 9 countries across the world will be invited to participate in this study and approximately 32 of these patients will come from the UK. It is a privately funded study. The study sponsor is called Teva Pharmaceuticals Industries Ltd.
What is Crohn's Disease?
Crohn's Disease is a long term illness that causes inflammation of the gut. It can affect any part of the digestive system from mouth to anus but most often the small intestine and the colon. Symptoms occur when part of the gut becomes inflamed. These symptoms may include diarrhoea, abdominal pain, fever and weight loss. For more information please view www.nacc.org.uk.
What is the new investigational drug that is being tested?
Laquinimod is a man-made chemical compound that has been developed for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS). Multiple Sclerosis (MS) is an inflammatory neurological disease. Laqunimod has previously been tested in Phase I (healthy volunteer) and Phase II clinical trials (testing in people with RRMS). Laquinimod has not been used to treat Crohn's disease patients before.
Laquinimod is an oral (given by mouth) drug and is supplied as white capsules and will be taken by mouth with water, once a day.
The way laquinimod works is still under investigation. What is known, so far, is that laquinimod may change the immune response (the way the body fights infection) which causes the inflammation, and therefore may help in diseases with too much inflammation, such as Crohn's disease.
Approximately 595 people, including healthy volunteers and patients with MS have taken laquinimod during clinical trials. Two large MS studies investigating the safety and effectiveness of laquinimod are ongoing.
Will everyone receive the new investigational drug called laquinimod?
No.
In each of the four different dose groups, two thirds of the participants will receive the new drug laquinimod. One third of participants will receive dummy capsules (or placebo) that does not contain any active ingredient. Therefore, you will have a 66.6% chance of receiving active drug. The treatment that you will receive is decided randomly by a computer programme. Neither you nor your study doctor will know what treatment you are receiving during the study (this is called a double-blind study). However, should it need to be known, for example, if you experience a serious side effect to the study medication, your study doctor can find out what you are receiving.
What do we know about the safety of laquinimod from clinical trials performed to date?
Laquinimod has not been used to treat Crohn's disease patients before. However, in previous clinical trials in patients with Multiple Sclerosis, laquinimod was found to be well tolerated. The most common side effects and discomforts reported by participants were: insomnia (difficulty sleeping), chest pain, stomach pain, back pain, sinus infection, tonsillitis (throat infection), sore throat, urinary tract infection, menstrual (period) pain, headaches, dizziness, fast heart beat, nausea and vomiting, upper respiratory tract infection, joint pain and herpes virus infections. Some changes in the blood tests, which can be early signs of inflammation (swelling) or potential liver problems and a decrease in haemoglobin (the oxygen carrier in the blood), sometimes leading to mild anaemia were also reported. In general, these changes did not require the experimental drug to be stopped. It is important to remember that these side effects are only the most common ones reported to date, and individual participants may suffer from additional and different side-effects. It is important that you ask your study doctor questions about the potential risks and disadvantages before agreeing to participate in this study.
What do I have to do if I am interested in participating in the study?
Firstly, talk to the consultant and medical team who are responsible for your care. You will need to read the Patient Information Leaflet very carefully. This leaflet will explain all of the details about the study (including possible side effects and risks), however, please ask questions about anything you don't understand. If you agree to participate and before you enter the study, you will be asked to sign two consent forms. One copy will be given to you to keep and your study doctor will keep the other. The informed consent form is not a contract - please remember that you have the right to leave the study at any time, for any reason.
How long will my participation in the study last?
Each different dose group will be studied for 14 weeks. This is made up of a screening phase of 1- 2 weeks followed by 8 weeks of treatment with either active study drug or placebo, and 4 weeks later, an end of study visit at Week 12. You will be asked to attend for eight clinic appointments throughout this 14 week period.
What is the screening visit?
If you agree to take part in this study you will be asked to attend the hospital for what is known as a screening visit. This visit may take up to 4 hours. The aim of the screening visit is to see whether you are eligible to take part in the study. In order to determine whether you fulfill all criteria for participation in this study, your study doctor will record your complete medical history, your Crohn's disease history and related signs/symptoms as well as any previous or current treatment drugs. In addition, a physical examination will be performed. If you have a fistula between the intestine and the skin, then your study doctor will lightly press on it to check how it drains. In addition, in order to see if you are suitable to take part in this study, your study doctor may advise that you need to have an endoscopy performed. However, this is not a madatory study procedure and your study doctor will discuss this fully with you.
Blood and urine tests, a pregnancy blood test (for women of childbearing potential), vital signs (blood pressure, pulse, temperature and weight), electrocardiogram (ECG) which is a simple test of your heart's rhythm, and a chest X-ray (if not performed in the last 6 months) will also be performed. You will have been given a collection pot by your study doctor so you can bring a stool sample to this visit for testing. This test is to exclude the probability of intestinal bacterial inflammation (tummy bug). You will also be reminded to bring a stool sample with you for the next visit. If possible, the stool sample should be collected on the morning of your visit.
If all your medical examinations and blood results obtained at the screening visit are suitable, you will be invited to attend another visit about 1-2 weeks later called the baseline visit. At the screening visit you will receive Crohn's Disease Activity Index (CDAI) diary cards, which you will be asked to complete every day until your next scheduled baseline visit and later on during the entire study period. You will be shown how to complete these cards during your first few visits. The CDAI diaries are very important and following the exact instructions is crucial for determining your suitability to participate in the study as well as evaluating your Crohn's disease progression throughout the study.
What is the baseline visit?
At this visit (baseline visit), your study doctor will collect your CDAI diaries, review the results of all tests performed at your previous visit, perform a physical examination and determine your final suitability to participate in the study. This visit is expected to last up to 4 hours. At this visit and before you receive any treatment drug (laquinimod or placebo) your vital signs will be taken again, along with a physical examination, ECG, urine and blood tests will also be repeated. Some of your urine and a small amount of blood will be tested to ensure you are not pregnant if you are a woman of child bearing potential. If your urine pregnancy test is positive at this visit then you will not be able to participate in the study.
You will be asked not to eat 12 hours before this visit. This is so a blood sample can be taken to measure the lipids (fat levels) in your blood. A light snack will be provided once this blood sample is taken.
You will also be asked to provide a stool sample. This will be used for measuring a protein called calprotectin which can show how much inflammation is occurring in your gut. If you have a fistula between the intestine and the skin, then your study doctor will lightly press on it to check how it drains. If the test measurements made during this visit are acceptable you will receive your treatment drug (laquinimod or placebo).
What will I have to do during subsequent study visits?
At the subsequent study visits (Weeks 1, 2, 4, 6 and 8) your study doctor will check how you are getting on with your study medication, perform the study related assessments and will review your general health and well-being and collect your CDAI diaries. The assessments performed at each visit vary slightly, however, may include a physical examination, ECGs, testing of blood and urine samples, blood pressure and temperature checks. You will be asked to bring a stool sample with you to each of these visits. In addition to these scheduled study visits, you will be able to attend the clinic for any reason during the course of the study.
What happens at the end of the study?
At the end of the study you will have one final visit (week 12). If you discontinue with the study, either because you have decided to withdraw or the study doctor or Teva has decided that you should not be in the trial anymore, you will be asked to attend for a termination visit to end your participation in the study. Your study doctor will discuss alternative treatment and care options with you when you complete the study.