FOR HEALTHCARE PROFESSIONALS
The YELLOWSTONE Study Programme
Dear Sir or Madam,
Thank you for your interest in the YELLOWSTONE Study Programme for Crohn’s disease patients.
The YELLOWSTONE Study Programme is a multicentre phase III clinical trial evaluating the efficacy and tolerability of ozanimod (also known as RPC1063). The investigational drug, ozanimod, is an orally administered S1P (sphingosine-1-phosphate) receptor modulator evaluated for efficacy in treating patients with moderate to severe, active Crohn’s disease.
This website is designed to give you all the essential information you need about the investigational drug ozanimod and the YELLOWSTONE Study Programme. In particular, the randomised, double-blind and placebo-controlled induction study is described. You will also have the opportunity to receive further information material for your practice and your patients.
Could ozanimod be an alternative for a patient you are currently treating for Crohn’s disease? If you recommend clinical trial participation, your patients are welcome to contact our Patient Information Service. They will discuss the possible next steps for study participation. This is completely non-binding for your patients.
Thank you for your support.
Yours sincerely,
STUDY MANAGEMENT
The national coordinating investigator of the YELLOWSTONE Study Programme
Poland
Prof. dr hab. n. med.
Krystyna Stec-Michalska
Specjalista chorób wewnętrznych i gastroenterologii
Centrum Opieki Zdrowotnej Orkan-Med., Ksawerów
Poland
Prof. dr hab. n. med.
Marek Woynarowski
Specjalista chorób pediatrii i gastroenterologii
Centrum Zdrowia MDM, Warszawa
Content
OVERVIEW
What is the YELLOWSTONE Study Programme?
The most important inclusion criteria
- Symptoms that have been present for at least 3 months and are compatible with the diagnosis of Crohn’s disease.
- moderate to severe, active Crohn’s disease.
- CDAI ≥ 220 and ≤ 450.
- average daily stool frequency ≥ 4 and/or abdominal pain score ≥ 2.
- SES-CD score ≥ 6 or, in the case of isolated ileal involvement, SES-CD score ≥ 4,
- inadequate response, loss of response or intolerance to at least one of the following therapies: Corticosteroids, immunomodulators, biologics.
OZANIMOD
Background information on the investigational drug ozanimod
- Ozanimod is an oral agent that is swallowed as a capsule.
- Ozanimod is a sphingosine-1-phosphate (S1P) receptor modulator that selectively binds to sphingosine-1-phosphate receptor subtypes 1 and 5.
- Ozanimod leads to lymphocyte retention in lymphoid tissues and thus to a decrease in lymphocytes in the peripheral blood. This could result in reduced migration of lymphocytes to sites of inflammation, which could improve chronic inflammation.1
- Immune surveillance is expected to be maintained.2
- Ozanimod (Zeposia®) has been approved in the USA since March 2020 and in Europe since May 2020 (in Switzerland since August 2020)3 for the treatment of relapsing-remitting multiple sclerosis (RRMS).4,5
- The FDA approved Ozanimod for the treatment of ulcerative colitis in May 2021.6 The European authorities are also reviewing the approval.
- Ozanimod is in clinical trials for Crohn’s disease.
The mechanism of action of ozanimod
Results of clinical trials of ozanimod in Crohn's disease and ulcerative colitis to date
Results in ulcerative colitis
- Study design: multicentre, randomised, double-blind, placebo-controlled trial of ozanimod in patients with active moderate-to-severe ulcerative colitis (Total Mayo Score 6-12) receiving aminosalicylates, prednisone (≤20 mg/day), and/or budesonide MMX.
- Evidence of efficacy: The primary endpoint of clinical remission was achieved after the induction phase at week 10 and in the maintenance phase at week 52. Statistically significant differences between ozanimod and placebo were also shown for the secondary endpoints of clinical response, endoscopic improvement and (histo-endoscopic) mucosal healing.
- Safety profile: Safety and tolerability were comparable to the known safety profile of ozanimod in MS. No other safety signals were identified.
The unblinded extension study of TRUE NORTH is still ongoing and is expected to be completed in the first quarter of 2022.
Results in Crohn's disease
Results from the STEPSTONE phase II clinical trial on Crohn’s disease:
- Study design: multicentre open-label study of ozanimod in patients with active moderate-to-severe Crohn’s disease (CDAI score 220-450), with inadequate response, loss of response or intolerance to at least one prior therapy.
- Proof of efficacy: Endoscopic, histological and clinical improvements after 12 weeks of treatment with 1 mg ozanimod.
- Safety profile: The overall safety profile of ozanimod in Crohn’s disease was comparable to that in ulcerative colitis. No other safety signals were identified.
STUDY PROGRAMME
Overview of the study design
- The YELLOWSTONE induction studies:
Two identical 12-week clinical trials comparing the efficacy, safety and tolerability of the investigational drug ozanimod versus placebo in patients with moderate to severe active Crohn’s disease. The primary objective is to induce clinical remission at week 12 in patients with active clinical symptoms. Patients will be randomised in a 2:1 ratio to ozanimod or placebo. CDAI and endoscopic data will be collected at baseline and week 12.
- The YELLOWSTONE maintenance study:
A 52-week clinical trial to compare the efficacy, safety and tolerability of maintenance therapy with the investigational drug ozanimod versus placebo in patients with moderate-to-severe active Crohn’s disease and clinical response in the YELLOWSTONE induction studies. Approximately 410 study participants who received and responded to ozanimod in the induction studies will be randomly assigned in a 1:1 ratio to ozanimod 1 mg or a placebo. Around 75 participants from the placebo group in the induction studies who have a clinical response will continue to receive the placebo. CDAI and endoscopic data will be collected at the end of the maintenance study (week 64 of treatment, including induction). Patients who experience a flare-up of their Crohn’s disease during the maintenance study will be given the option to end the maintenance study early and participate in the open-label YELLOWSTONE extension study.
- The unblinded YELLOWSTONE extension study:
A clinical trial to investigate the long-term safety and efficacy of the investigational drug ozanimod in treating patients with moderate to severe, active Crohn’s disease. This study is open to patients who have already participated in either of the other YELLOWSTONE sub-studies and have either failed to achieve a clinical response in one of the YELLOWSTONE induction studies or have experienced a Crohn’s disease flare-up in the YELLOWSTONE maintenance study. All study participants will receive the investigational drug ozanimod 1mg in an unblinded fashion. The study duration is estimated to be approximately 234 weeks (4.5 years).
STUDY SITES
This is where the YELLOWSTONE Study Programme takes place
POLAND
32
Locations
WORLDWIDE
1,200
Participants
POLAND
32
Locations
WORLDWIDE
1,200
Participants
A Patient Information Service is available for the YELLOWSTONE Study Programme, which is happy to provide interested patients with non-binding information about the clinical trials.
STUDY SITES
This is where the YELLOWSTONE Study Programme takes place
The most important inclusion criteria
Please recommend patients aged 18 to 75 years who meet the following criteria:
- Symptoms that have been present for at least 3 months and are compatible with the diagnosis of Crohn’s disease,
- moderate to severe, active Crohn’s disease,
- CDAI ≥ 220 and ≤ 450,
- average daily stool frequency ≥ 4 and/or abdominal pain score ≥ 2,
- SES-CD score ≥ 6 or, in the case of isolated ileal involvement, SES-CD score ≥ 4,
- inadequate response, loss of response or intolerance to at least one of the following therapies: Corticosteroids, immunomodulators, biologics.
Patients who have already received four different biologics to treat their Crohn’s disease cannot participate in the study. The examinations to check the criteria are carried out at the study site at the beginning of the study participation.
SPONSOR
About Celgene
DOWNLOADS
Information material for your practice
If you would like further information material for yourself or your practice, the following documents are available:
KONTAKT
For medical professionals
For specialist medical information, please contact Bristol Myers Squibb’s Medical Information department.
Bristol Myers Squibb
Medical Information
For specialised medical information:
www.globalbmsmedinfo.com
Special enquiries about the study:
informacja.medyczna@bms.com
For patients
The patient information service of the YELLOWSTONE Study Programme is available for interested patients.
Patient Information Service of the YELLOWSTONE Study Programme
RECOMMEND PATIENTS
How to refer a patient to the YELLOWSTONE Study Programme
If you would like to refer a patient for the YELLOWSTONE Study Programme, please instruct them to complete the online patient questionnaire. The questionnaire addresses the most important inclusion and exclusion criteria in patient-friendly language.
If your patient is eligible, they will receive further information and can have a personal conversation with the Patient Information Service of the YELLOWSTONE Study Programme. We will discuss with the patient what the possible next steps are for study participation. This procedure is entirely non-binding for your patient.
- Prescribing information Zeposia, https://fi.b-ms.de/zeposia (last accessed June 2021)
- Harris, et. al, Neurol Neuroimmunol Neuroinflamm Sep 2020, 7 (5) e839; DOI: 10.1212/NXI.00000000000839
- Approval of Zeposia in Switzerland, https://www.swissmedic.ch/swissmedic/de/home/humanarzneimittel/authorisations/new-medicines/zeposia_hartkapseln_ozanimodum.html (last accessed June 2021)
- Bristol Myers Squibb. Press Release. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis. 26 March 2020. https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-bristol-myers-squibbs (last accessed April 2020)
- European Medicines Agency: Assessment Report Zeposia. 9 April 2020. https://www.ema.europa.eu/en/documents/assessment-report/zeposia-epar-public-assessment-report_en.pdf (last accessed August 2020)
- Bristol-Myers Squibb. Press Release. https://news.bms.com/news/corporate-financial/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Zeposia-ozanimod-an-Oral-Treatment-for-Adults-with-Moderately-to-Severely-Active-Ulcerative-Colitis1/default.aspx (last accessed June 2021)