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Investigational drug

An investigational drug is a medicine not yet approved for a specific disease. It is therefore being studied in clinical trials for the treatment of said specific disease. The active substance contained in the investigational drug may be already approved for treating other diseases.

In patients with Crohn’s disease, certain signalling molecules cause more immune cells to migrate into the intestinal mucosa, accumulate there and promote inflammation. The investigational drug leads to a certain type of immune cells (especially T cells) no longer being able to leave the lymphatic tissue. Scientists assume that this also means that fewer of these cells can migrate into the intestinal mucosa. This may reduce the inflammation in the gut.
Yes. The investigational drug is suitable for treating various diseases involving chronic inflammation caused by an overactive immune system. These diseases include the chronic inflammatory bowel disease ulcerative colitis or the neurological disorder multiple sclerosis (short: MS). In total, more than 5,000 people have already received the active substance within various clinical studies. The active substance has been approved to treat relapsing-remitting multiple sclerosis (RRMS) in the USA, Europe and Switzerland since 2020.1,2,3 In addition, the phase III study programme in ulcerative colitis was completed this year. In this trial, the active substance was able to significantly and sustainably improve symptoms. Since May 2021, it has also been available to patients with ulcerative colitis in the USA4. The European authorities are currently reviewing the application for approval. And: There are preliminary results from a phase II study in the treatment of patients with Crohn’s disease, which indicate that the investigational drug could be effective and tolerable as well5. In order for the investigational drug to be approved in the treatment of Crohn’s disease, we are now conducting the phase III trials as part of the YELLOWSTONE Study Programme.
No. The study drug is swallowed as a capsule. One capsule per day is taken during the study participation.
Yes, this is generally possible, but it depends on the medication you are currently taking. If you qualify to take part in the study, your study doctor will again clarify with you whether you can continue to take your current medication. If you wish, you can also involve your treating doctor in the decision-making process. Generally, common medicines for Crohn’s disease, such as aminosalicylates or cortisone, can still be taken in a certain dosage as basic therapy. However, the dose of these medications must not be changed, at least during the induction study.
Generally speaking, side effects can always occur when taking medicines. In approved medicinal products, the frequency of possible side effects is largely known and is stated in the package leaflet. In the case of investigational medicinal products still in clinical trials, adverse events may occur that cannot be predicted. Therefore, study participants are monitored intensively and closely to be able to act quickly in such cases. The study is reviewed and approved in advance by the responsible federal authority and an ethics committee. In addition, the study doctor will also discuss the possible known side effects with you in detail – and what to do in case of adverse events. Several previous studies have shown that the investigational drug has a balanced tolerability profile so far.1,2,6,7 In total, more than 5,000 people have already received the investigational drug within the various clinical trials. Side effects experienced so far include: Colds, runny nose, sore throat, and inflamed throat, reduced number of specific white blood cells (T cells) in the blood (due to the mechanism of action), urinary tract infections, increased liver enzyme levels and increased blood pressure. The frequency of side effects was comparable in both the investigational drug and placebo groups.1

YELLOWSTONE Study Programme

The phase III clinical trials investigate the efficacy and tolerability of the investigational drug in treating moderate to severe Crohn’s disease. Patients with this disease have an over-reactive immune system. The investigational drug prevents pro-inflammatory immune cells of the immune system (T cells) from entering the bloodstream from the lymphatic tissue and subsequently migrating into the intestinal mucosa. This should reduce chronic inflammation in the gut. The YELLOWSTONE Study Programme aims to find out how well the investigational medicine works and how tolerable it is.

The YELLOWSTONE Study Programme includes three phase III clinical trials: an entry study (also called induction study), a maintenance study, and an open-label extension study. If you want to participate in the YELLOWSTONE Study Programme, you will first start with the induction study. Then, depending on your clinical improvement and together with the investigator, you decide whether you wish to continue in the study programme.

In the induction study, the effectiveness of the investigational drug is compared to a placebo (= sham drug). You are randomly assigned to the groups, and neither you nor your study doctor knows which group you are in. If there is a “clinical response” after the induction study, i.e. your symptoms and the colonoscopy findings have improved significantly, you can continue your study participation in the maintenance study. This study aims to determine whether the effects of the induction study continue or even improve. However, if your symptoms do not improve (sufficiently) during the induction study, you have the option of entering the open-label extension study. Here, you will definitely receive the investigational medicine containing the active substance.

In the maintenance study, the investigational drug is compared again with placebo. If you suffer a disease relapse during this time, you also have the option of entering the open-label extension study. In addition, you can stop the study prematurely at any time.

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The YELLOWSTONE Study Programme consists of phase III clinical trials, which means that the investigational drug is administered to the largest possible number of patients to investigate the therapeutic benefit and side effects. In the induction study, the investigational medicine or the placebo will be administered to a total of 1,200 people with moderate to severe Crohn’s disease worldwide. It is called a randomised, placebo-controlled and double-blind study. The efficacy is evaluated based on specific criteria. These include certain blood values, the findings of your intestinal mucosa in the colonoscopy, as well as the manifestations of symptoms, which are determined using special disease activity values. Placebo-controlled means that the effect of the investigational drug is tested in comparison to a placebo. A placebo looks exactly like the drug being tested, but does not contain any active ingredient. Randomised means that chance decides whether you get the investigational drug or a placebo. This is to avoid any influence in the allocation process. Randomisation takes place at the beginning of the treatment phase. Double-blind means that neither the members of the study team nor you will know which treatment you will be assigned to. So no one can tell you whether you will get a placebo or an active substance. The purpose of “blinding” in trials is to prevent members of the trial team or the trial participants from influencing the results. For example, just the expectation that the medicine will help can influence what a participant says about their symptoms.

All new medicines must first be tested in clinical trials before they can be released for general treatment. In these studies, the safety, tolerability and efficacy of the new drug are tested. Strict guidelines apply and doctors closely monitor the participants. For patients, participation in clinical trials means that they have the opportunity to receive a new active substance for the treatment of their Crohn’s disease even before it is officially approved.

The clinical trials are divided into three phases:

Phase I: An investigational drug is administered to a small group of healthy volunteers for the first time. This is done starting with a very low dose, which is then carefully increased. The aim is to investigate tolerability and safety.

Phase II: A somewhat larger group of patients receives the investigational drug. In addition to safety and tolerability, efficacy is tested here.

Phase III: The investigational drug is tested in large, often international clinical trials involving several hundred to thousands of patients. Safety, tolerability and efficacy are tested. With the results of all these studies, marketing authorisation can be applied for the investigational drug. If successful, it becomes an officially approved drug that is now available to patients.

Phase IV: Sometimes, an additional study phase is appended after the drug has been approved. More information can be gained this way, e.g. about side effects, clinical benefits and safe use in everyday clinical practice.

The study programme has already started and is expected to run until 2025, so participation is possible from now on. Here, you can easily check whether you are generally eligible for the induction study without any obligation.

The YELLOWSTONE induction study has a 2:1 ratio of investigational drug to placebo. So the probability that you will receive the investigational drug containing the active substance is 67 per cent (2 out of 3). The probability that you will receive the placebo is 33 per cent. In the maintenance study, the investigational drug is also controlled with placebo using a ratio of 1:1. Here, the probability for receiving either the investigational drug and the placebo is, therefore 50 per cent each. If you have received a placebo during the induction study and showed a clinical response, you will continue to take a placebo during the maintenance study.
Neither you nor your study doctor or anyone else involved in the study will be told which treatment you are receiving. This is also called “blinding”.

In certain situations, such as a medical emergency, you may be unblinded. This means that your study doctor or the study team will then learn whether you are receiving the study drug or placebo.

Study participation

The study programme takes place worldwide. Also in Germany, Switzerland, Austria, and the United Kingdom more than 30 study sites are involved. These are renowned clinics and competent specialist practices whose principal investigators are specialists in treating inflammatory bowel diseases.
With our questionnaire you can easily check without obligation whether you are generally eligible for the study.

The treatment period of the study lasts 12 weeks. In total, your participation in the induction study will last four to seven months – including all pre- and post-treatment examinations. During this time, you will need to take about six to eight trips to your study site.

The study lasts seven months if you complete the study programme afterwards. In the beginning, there is a preliminary examination. Usually, after about one month, all results are available, and you can start the treatment phase of about three months (12 weeks). About one and three months after the end of the treatment phase, two follow-up examinations take place.

If you decide to continue participating in the study (maintenance or extension study) after the 12-week treatment phase, the follow-up examinations at this point will be omitted. The duration of the induction study is then reduced to about four months, and you can enter directly into one of the follow-up studies.

No, as part of the YELLOWSTONE Study Programme you will visit the study site on an outpatient basis.

No, you do not have to pay anything to participate in these studies. The study sponsor bears the costs of the medication administered in the study and those of all examinations and laboratory analyses. To a certain extent, travel and meal costs may also be covered. Celgene, a Bristol Myers Squibb company, is the sponsor of the YELLOWSTONE Study Programme. In addition, the sponsor’s study participant insurance covers possible risks of study participation.

NHS has no influence on your participation in the study. Only costs related to your medical care that you would receive even without participating in the study programme will be charged to NHS.

After the end of the entry study, also called the induction study, you have the possibility to continue participation in the study programme. This depends, among other things, on how the study doctor assesses your disease activity after completion of the induction study: If your disease has improved significantly and you show a clinical response, you have the option of taking part in the maintenance study. This is also placebo-controlled and is intended to confirm that the treatment effects continue or even improve further. If your symptoms have not improved significantly after the end of the induction study, you may have the option of switching to an open-label extension study, in which you will receive the investigational drug containing the active substance in any case.
Yes, as soon as the clinical trial results are available, you can ask for them at your study site. You will also find out which treatment group you were assigned to (investigational drug or placebo). The study results are also available on websites like www.clinicaltrials.gov ,for example. This will happen when all patients have been through the induction and maintenance study and the data have been analysed (probably in 2024).

Yes. Consult your study doctor about how to inform your doctor about your participation in the study programme and the results.

The overall results of the study programme will be communicated by your study site as soon as the studies are completed and the data are officially available.

Yes, you have the right to terminate your participation at any time. You do not have to give a reason for this. This will not cause you any disadvantages concerning further medical care.
However, you should inform your study doctor immediately about your decision. It is also important to report any abnormalities that may have occurred during the study programme so that appropriate conclusions may be drawn for both you and other participants in the study programme.

If it is necessary for your safety, the study doctor may withdraw you from the study programme. In this case, the study team will discuss possible further treatment with you.
Celgene, a Bristol Myers Squibb company and the sponsor of the study programme, also reserves the right to stop the YELLOWSTONE Study Programme prematurely. This may be the case, for example, if an interim evaluation shows that the treatment is not effective.

The privacy of persons involved in a clinical trial is protected to the highest degree. To this end, your data is pseudonymised. This means that the study doctor collects information from you and labels it with a code. In this way, your data is processed – and without any information that might reveal your identity. Only authorised persons, such as the study doctor, have access to the list of patient names and the corresponding codes.

Patient Information Service

Celgene, a Bristol Myers Squibb company, is sponsoring the study programme. Bristol Myers Squibb is a global BioPharma company dedicated to discovering, developing, and using innovative medicines that help patients overcome serious diseases. For further information please visit www.bms.com/gb.

Celgene has commissioned Trials24 GmbH to develop and maintain the website www.crohns-study.co.uk, online questionnaire, and Patient Information Service for the YELLOWSTONE Study Programme. Trials24 GmbH is based in Munich, Germany. It is a specialised service provider and supports biopharmaceutical companies in finding participants for clinical trials to make innovative drugs available to patients more quickly.

With the questionnaire you can check easily and without obligation whether you are eligible for taking part in a study. If you have any further questions, you can contact the Patient Information Service or the study sites. You can reach our Patient Information Service by e-mail at info@crohns-study.co.uk or via the contact form or give us a call Monday to Friday from 9:00 to 18:00 under the telephone number United Kingdom: +44 20 3608 2093

Are you interested in the YELLOWSTONE Study Programme?

Find out now, without obligation, via our questionnaire whether you are eligible for study participation.