Extension study of oral Ozanimod in patients with moderate to severe active Crohn's disease

Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Moldova, Republic of, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States (ICTRP)

ID di studio ICTRP
EUCTR2017-004295-55 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A Phase 3, Multicenter, Open-Label Extension Study of Oral Ozanimod for Moderately to Severely Active Crohn’s Disease (BASEC)

Titolo accademico
A Phase 3, Multicenter, Open-Label Extension Study of Oral Ozanimod for Moderately to Severely Active Crohn?s Disease (ICTRP)

Titolo pubblico
Multicenter Extension Study of Oral Ozanimod in patients with Moderately to Severely Active Crohn?s Disease (ICTRP)

Malattie studiate
Moderately to Severely Active Crohn?s Disease
MedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders;Therapeutic area: Diseases [C] - Digestive System Diseases [C06] (ICTRP)

Intervento studiato

Product Name: ozanimod
Product Code: RPC1063 (equivalent to ozanimod HCl)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Other descriptive name: OZANIMOD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Product Name: ozanimod
Product Code: RPC1063 (equivalent to ozanimod HCl)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Other descriptive name: OZANIMOD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

Inclusion criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subjects who are not in clinical response and/or clinical remission after completing 12 weeks in the Induction Studies RPC01-3201 or RPC01-3202, subjects who experience relapse in the Maintenance Study RPC01-3203, subjects who complete the Maintenance Study RPC01-3203, subjects who complete at least 1 year of RPC01 2201.
2. Subject must provide written informed consent prior to any study-related procedures, and have the ability to comply with the Table of Events. For adolescents, a parent/legal guardian of the adolescent must sign the informed consent form. In addition, adolescent subjects must also agree to participate in the study by signing an assent form. A parent or guardian must be willing to supervise adherence to the protocol requirements. Adolescent subjects who reach the legal age of consent while participating in the study will be asked to sign an ICF themselves to acknowledge their willingness to continue in the study.
3. Female subjects of childbearing potential:
Note: For the purposes of this study, a female subject is considered to be of childbearing potential if she is = 12 years of age or has reached menarche, whichever occurred first, and 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
Must agree to practice a highly effective method of contraception throughout the study until completion of the 90-day Safety Follow-up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl Index of less than 1% per year when used consistently and correctly. Examples of acceptable methods of birth control in the study are the following:
? combined hormonal (containing oestrogen and progestogen) contraception, which may be oral, intravaginal, or transdermal
? progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
? placement of an intrauterine device (IUD)
? placement of an intrauterine hormone-releasing system (IUS)
? bilateral tubal occlusion
? vasectomised partner
? complete sexual abstinence
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted for female subjects of childbearing potential. The Investigator will educate all FCBP about the different options of contraceptive methods or abstinence at Day 1, as appropriate. The subject will be re-educated every time her contraceptive measures/methods or ability to become pregnant changes. The female subject?s chosen form of contraception must be effective by the time the female subject starts the study (for example, hormonal contraception should be initiated at least 28 days before Day 1).
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age r (ICTRP)

Exclusion criteria:
The presence of any of the following will exclude a subject from enrollment:
4.3.1. Exclusions Related to General Health:
1. Subject has any clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study
2. Subject is pregnant, lactating, or has a positive urine beta human chorionic gonadotropin (?-hCG)
3. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated
4.3.2. Exclusions Related to Medications:
4. Hypersensitivity to active ingredients or excipients of ozanimod
5. Subject has received any of the following therapies since the first dose of IP in the prior ozanimod study:
? treatment with a biologic agent as well as other treatments for CD such as etrasimod, filgotinib, upadacitinib
? treatment with an investigational agent other than ozanimod
? treatment with D-penicillamine, leflunomide, thalidomide, natalizumab, fingolimod or other S1P modulators
? treatment with lymphocyte-depleting therapies (eg, Campath?, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab)
6. Subject is currently receiving or requires initiation of any of the following therapies:
? treatment with corticosteroids at a dose that exceeds the prednisone equivalent of >40 mg
? treatment with immunomodulatory agents (eg, azathioprine, 6-MP, or methotrexate)
? chronic non-steroidal anti-inflammatory drug (NSAID) use (note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is permitted)
? treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with 2 or more agents in combination known to prolong PR interval
? treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
7. Subject is receiving treatment with any of the following drugs or interventions within the corresponding timeframe:
? CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) and inducers (eg, rifampicin)
? Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
4.3.3. Exclusions Related to Laboratory Results:
8. Subject has any clinically significant abnormality ECG results which in the opinion of the investigator may put the subject at risk.


Endpoint primari e secondari
Primary end point(s): Key Efficacy Endpoints:
? Proportion of subjects with a CDAI score of < 150
? Proportion of subjects with a simple endoscopy score (SES-CD) decrease from baseline of = 50%
? Proportion of subjects with average daily abdominal pain score = 1 point, and average daily stool frequency = 3 points with abdominal pain and stool frequency no worse than baseline
? Proportion of subjects with CDAI reduction from baseline of = 100 points or CDAI score of < 150
? Proportion of subjects with absence of ulcers = 0.5 cm with no segment with any ulcerated surface = 10%
? Proportion of subjects with CDAI reduction from baseline of = 70 points
? Change from baseline in CDAI
? Proportion of subjects with CDAI reduction from baseline of = 100 points or CDAI score of < 150 and SES-CD decrease from baseline of = 50%
? Proportion of subjects with CDAI score of < 150 and SES-CD = 4 points and a SES CD decrease = 2 points
? Proportion of subjects with average daily abdominal pain score = 1 point and average daily stool frequency = 3 points and a stool frequency no worse than baseline and SES-CD = 4 points and a SES-CD decrease = 2 points
? Proportion of subjects with SES-CD = 4 points and a SES-CD decrease = 2 points
? Proportion of subjects with a CDAI score < 150 in subjects off corticosteroids
? Proportion of subjects with a Crohn?s Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of = 50%
Key Efficacy Endpoint specific to adolescents:
? Proportion of subjects with a PCDAI score of = 10 points
Exploratory Endpoints:
? Proportion of subjects with average daily abdominal pain score = 1 point, average daily stool frequency = 3 points with abdominal pain and stool frequency no worse than baseline, and SES-CD decrease from baseline = 50%
? Proportion of adolescent subjects with a decrease from baseline in PCDAI score = 15 points.
? Change from baseline in weight, body mass index (BMI), height, and height velocity z-scores (adolescents only)
? Change from baseline in PCDAI score and weighted PCDAI score (adolescents only)
? Efficacy in subjects (clinical response, clinical remission, and endoscopic improvement) as a function of baseline and change-from-baseline in biomarkers (eg, C-reactive protein, fecal calprotectin, high-density lipoprotein, IgA, IL-7, collagen fragments);Timepoint(s) of evaluation of this end point: Due to the open-label nature of the study and the lack of a control group, all data will be summarized and no hypothesis testing will be performed. Each efficacy endpoint will be summarized and 95% confidence intervals around the estimates may also be presented. All efficacy data will be listed.
For all proportion-based efficacy endpoints, subjects with missing efficacy data will be considered non-responders.
For continuous efficacy endpoints, subjects with missing data will have their last post baseline value carried forward.
Observed-cases analyses will also be presented for all efficacy endpoints.
;Main Objective: The objective of this study is to demonstrate the long-term safety and explore long-term efficacy of ozanimod for the treatment of subjects with moderately to severely active CD.;Secondary Objective: Not applicable (ICTRP)

Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable (ICTRP)

Data di registrazione
08.03.2018 (ICTRP)

Inclusione del primo partecipante
08.08.2018 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Keith Usiskin, kusiskin@celgene.com, +19088976550, Celgene International II S?rl (ICTRP)

ID secondari
RPC01-3204, 2017-004295-55-HU (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004295-55 (ICTRP)