Clinical Trials List
Protocol NumberRPC01-3202
NCT Number(ClinicalTrials.gov Identfier)NCT03440385
2018-04-01 - 2020-04-01
Phase III
Recruiting5
ICD-10K56.69
Other intestinal obstruction
ICD-10K50.90
Crohn's disease, unspecified, without complications
ICD-10K50
Crohn's disease [regional enteritis]
ICD-9560.89
Other specified intestinal obstruction
Induction Study #2 - A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease
-
Trial Applicant
TAIWAN PSI HEALTH DEVELOPMENT COMPANY LIMITED
-
Sponsor
Celgene International II Sàrl
-
Trial scale
Multi-Regional Multi-Center
-
Update
2023/03/10
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 康瑞文 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Principal Investigator
Co-Principal Investigator
- Ming-Shiang Wu Digestive System Department
- 陳介章 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chien-Yu Lu Digestive System Department
- Wen-Hung Hsu Digestive System Department
- Chao-Hung Kuo Digestive System Department
- HSIANG YAO SHIH Digestive System Department
- Deng-Chyang Wu Digestive System Department
- Fang-Jung Yu Yu Digestive System Department
- Yu-Chung Su Digestive System Department
- I-CHEN WU Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Linkou Chang Gung Medical Foundation
Taiwan National PI
邱正堂
Co-Principal Investigator
- Ming-Yao Su Digestive System Department
- Puo-Hsien Le Digestive System Department
- 許振銘 Digestive System Department
- Chia-Jung Kuo Digestive System Department
- 林偉彬 Digestive System Department
- Cheng-Yu Lin Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Crohn’s disease, CD
Objectives
Confirm the role of oral ozanimod as an induction therapy in subjects with moderate to severely active CD (defined as Crohn’s Disease Activity Index [CDAI] score ≥ 220 to ≤ 450)
Test Drug
Ozanimod
Active Ingredient
Ozanimod HCl
Dosage Form
capsule
Dosage
0.25, 1
Endpoints
Primary objective:
Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical
remission
Secondary objectives:
Demonstrate the efficacy of ozanimod compared to placebo on induction of clinical
response, endoscopic response, endoscopic remission, and histologic improvement
Evaluate the efficacy of ozanimod compared to placebo, in subjects who had previously
received biologic therapy (eg, anti-IL-12, anti-IL-23, anti-TNF, or anti-integrin therapy)
Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical
remission and clinical response in adolescent subjects (aged 12 to 17 years, inclusive)
Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD)
relationship of ozanimod
Demonstrate the safety and tolerability of ozanimod as induction therapy
Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical
remission
Secondary objectives:
Demonstrate the efficacy of ozanimod compared to placebo on induction of clinical
response, endoscopic response, endoscopic remission, and histologic improvement
Evaluate the efficacy of ozanimod compared to placebo, in subjects who had previously
received biologic therapy (eg, anti-IL-12, anti-IL-23, anti-TNF, or anti-integrin therapy)
Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical
remission and clinical response in adolescent subjects (aged 12 to 17 years, inclusive)
Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD)
relationship of ozanimod
Demonstrate the safety and tolerability of ozanimod as induction therapy
Inclution Criteria
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female subjects aged 18 to 75 years (at Screening), inclusive (per regulation, in Taiwan this study is open to patients aged 20-75 only)
2. Subject must provide written informed consent prior to any study-related procedures, and have the ability to comply with the Table of Events
3. Subject has signs and symptoms consistent with a diagnosis of CD for at least 3 months (prior to first study drug administration). The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histology report. (Note: endoscopy and histopathology confirmation may be obtained during Screening if no prior report is readily
available)
4. Subject has met each of the following 2 criteria:
a CDAI score ≥ 220 and ≤ 450
an average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points
5. Subject has a SES-CD score of ≥ 6 (or SES-CD ≥ 4 in subjects with isolated ileal disease)
6. Subject has an inadequate response or loss of response to or is intolerant of at least 1 of the following CD treatments :
corticosteroids
immunomodulators
biologic therapy (eg, ustekinumab, TNFα antagonists, or vedolizumab)
7. If the subject is taking the following background therapies for CD, a stable dose must be maintained as indicated below:
oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) with a stable dose for at least 3 weeks prior to Screening endoscopy
prednisone (doses ≤ 20 mg per day) or equivalent with a stable dose for at least 2 weeks prior to Screening endoscopy
budesonide therapy (doses ≤ 9 mg per day) or beclomethasone doses ≤ 5 mg/day at a stable dose for at least 2 weeks prior to the Screening endoscopy
8. Subject at high risk (ie, family history, CD duration) for colonic malignancy has documented evidence of having had a surveillance colonoscopy within the last 2 years or according to local and national medical guidelines to evaluate for polyps, dysplasia, or malignancy. If there is no recent history of surveillance colonoscopy, this can be done as part of the colonoscopy performed during Screening. Any visualized adenomatous polyps must be removed and any suspicious lesion confirmed free of cancer and/or dysplasia prior to randomization.
9. (1) Female subjects of childbearing potential:
Must agree to practice a highly effective method of contraception throughout the study until completion of the 75-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. 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
sexual abstinence
(2) Male subjects:
Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the 75-day safety follow-up visit.
(3) All subjects:
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.
10. Subjects must have documentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody status or complete VZV vaccination at least 30 days prior to randomization.
Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female subjects aged 18 to 75 years (at Screening), inclusive (per regulation, in Taiwan this study is open to patients aged 20-75 only)
2. Subject must provide written informed consent prior to any study-related procedures, and have the ability to comply with the Table of Events
3. Subject has signs and symptoms consistent with a diagnosis of CD for at least 3 months (prior to first study drug administration). The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histology report. (Note: endoscopy and histopathology confirmation may be obtained during Screening if no prior report is readily
available)
4. Subject has met each of the following 2 criteria:
a CDAI score ≥ 220 and ≤ 450
an average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points
5. Subject has a SES-CD score of ≥ 6 (or SES-CD ≥ 4 in subjects with isolated ileal disease)
6. Subject has an inadequate response or loss of response to or is intolerant of at least 1 of the following CD treatments :
corticosteroids
immunomodulators
biologic therapy (eg, ustekinumab, TNFα antagonists, or vedolizumab)
7. If the subject is taking the following background therapies for CD, a stable dose must be maintained as indicated below:
oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) with a stable dose for at least 3 weeks prior to Screening endoscopy
prednisone (doses ≤ 20 mg per day) or equivalent with a stable dose for at least 2 weeks prior to Screening endoscopy
budesonide therapy (doses ≤ 9 mg per day) or beclomethasone doses ≤ 5 mg/day at a stable dose for at least 2 weeks prior to the Screening endoscopy
8. Subject at high risk (ie, family history, CD duration) for colonic malignancy has documented evidence of having had a surveillance colonoscopy within the last 2 years or according to local and national medical guidelines to evaluate for polyps, dysplasia, or malignancy. If there is no recent history of surveillance colonoscopy, this can be done as part of the colonoscopy performed during Screening. Any visualized adenomatous polyps must be removed and any suspicious lesion confirmed free of cancer and/or dysplasia prior to randomization.
9. (1) Female subjects of childbearing potential:
Must agree to practice a highly effective method of contraception throughout the study until completion of the 75-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. 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
sexual abstinence
(2) Male subjects:
Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the 75-day safety follow-up visit.
(3) All subjects:
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.
10. Subjects must have documentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody status or complete VZV vaccination at least 30 days prior to randomization.
Exclusion Criteria
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment or at the timepoint specified in the following criteria:
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 likely to require, in the physician's judgment, bowel resection within 12 weeks of entry into the study.
3. Subject has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has known strictures or stenosis leading to symptoms of obstruction
4. Subject has current stoma, ileal-anal pouch anastomosis, symptomatic fistula draining pusthat is likely to require, in the physician’s judgement, surgical or medical intervention within 12 weeks of entry into the study, or need for ileostomy or colostomy.
5. Subject has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome, or subject requires total parenteral nutrition
6. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated
7. Subject has documentation of a positive test for toxin producing Clostridium difficile (C. difficile), or polymerase chain reaction (PCR) examination of the stool on their most recent test, which must have been done in the past 60 days. If positive, subjects may be treated and retested no earlier than 7 days after completion of treatment.
8. Subject has documentation of positive examination for pathogens (ova and parasites, and bacteria), which must have been done in the past 60 days. If positive, subjects may be treated and retested.
9. Subject is pregnant, lactating, or has a positive serum beta human chorionic gonadotropin (β-hCG) measured during Screening.
10. Subject has clinically relevant cardiovascular conditions, making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study, including history or presence of the following:
Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III/IV heart failure, sick sinus syndrome, or severe untreated sleep apnea
Second degree atrioventricular (AV) Block , or third degree heart block unless subjects have a pacemaker in place
Prolonged QT corrected for heart rate using Fridericia's formula (QTcF) interval (QTcF > 450 ms males, > 470 ms females)
Resting heart rate (HR) <55 bpm when taking vitals as part of a physical examination at Screening
11. Subject has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c (HbA1c) > 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy
12. Subject has a history of uveitis (within the last year prior to Screening) or clinically confirmed diagnosis of macular edema
13. Subject has a known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease [excluding fungal infection of nail beds, minor upper respiratory tract infections, and minor skin infections]) or any major episode of infection that required hospitalization or treatment with intravenous (IV) antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening
14. History or known presence of recurrent or chronic infection (eg, hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus [HIV]); recurrent urinary tract infections are allowed
15. Subject has a history of active cancer within 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that have been excised and resolved); or colonic
dysplasia that has not been completely removed
16. Subject has a history of alcohol or drug abuse within 1 year prior to initiation of Screening
Exclusions Related to Medications:
17. Hypersensitivity to active ingredients or excipients of ozanimod or placebo
18. Subject has a history of primary nonresponse to 2 or more approved biologic therapies used for the treatment of CD
19. Subject has been treated with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is shorter) prior to the first dose of study drug
20. Subject has a history of treatment with an investigational agent within 5 elimination half-lives of that agent prior to the first dose of study drug
21. Subject has received a live or live attenuated vaccine within 4 weeks prior to the first dose of study drug
22. Subject has received previous treatment with lymphocyte-depleting therapies (eg, Campath®, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, or
daclizumab)
23. Subject has received previous treatment with D-penicillamine, leflunomide, or halidomide
24. Subject has received previous treatment with natalizumab or fingolimod
25. Subject has received previous treatment with oral cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of initiation of Screening
26. Subject has a history of treatment with IV immune globulin (IVIg), or plasmapheresis within 3 months prior to first dose of study drug
27. Subject has discontinued oral or rectal 5-ASA or corticosteroids within 2 weeks prior to the screening endoscopy.
28. Subject has planned concurrent treatment with immunomodulatory agents (eg,azathioprine, 6-MP, cyclosporine, or methotrexate) after randomization. Subjects receivingazathioprine, 6-MP, or methotrexate at screening must discontinue treatment with these agents prior to first dose of study drug
29. Subject has chronic nonsteroidal 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)
30. Subject treated with Class Ia or Class III anti-arrhythmic drugs or with 2 or more agents in combination known to prolong PR interval.
31. Subject receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
32. Subject is receiving treatment with any of the following drugs or interventions within the corresponding timeframe:
- At randomization
o CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) and inducers (eg, rifampicin)
- Two weeks prior to randomization
o Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
Exclusions Related to Laboratory Results:
33. Subject has screening ECG results showing any clinically significant abnormality.
34. Subject has serum creatinine results >1.4 mg/dL for women or > 1.6 mg/dL for men.
35. Subject has liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) results > 2 times the upper limit of normal (ULN), or direct bilirubin > 1.5 times the ULN.
36. Subject has a platelet count < 100,000/μL.
37. Subject has hemoglobin < 7.5 g/dL.
38. Subject has neutrophils < 1500/μL.
39. Subject has an absolute white blood cell (WBC) count <3500/μL.
40. Subject has an absolute lymphocyte count (ANC) < 800 cells/μL.
41. Subject has a forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) <70% of predicted values at screening
The presence of any of the following will exclude a subject from enrollment or at the timepoint specified in the following criteria:
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 likely to require, in the physician's judgment, bowel resection within 12 weeks of entry into the study.
3. Subject has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has known strictures or stenosis leading to symptoms of obstruction
4. Subject has current stoma, ileal-anal pouch anastomosis, symptomatic fistula draining pusthat is likely to require, in the physician’s judgement, surgical or medical intervention within 12 weeks of entry into the study, or need for ileostomy or colostomy.
5. Subject has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome, or subject requires total parenteral nutrition
6. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated
7. Subject has documentation of a positive test for toxin producing Clostridium difficile (C. difficile), or polymerase chain reaction (PCR) examination of the stool on their most recent test, which must have been done in the past 60 days. If positive, subjects may be treated and retested no earlier than 7 days after completion of treatment.
8. Subject has documentation of positive examination for pathogens (ova and parasites, and bacteria), which must have been done in the past 60 days. If positive, subjects may be treated and retested.
9. Subject is pregnant, lactating, or has a positive serum beta human chorionic gonadotropin (β-hCG) measured during Screening.
10. Subject has clinically relevant cardiovascular conditions, making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study, including history or presence of the following:
Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III/IV heart failure, sick sinus syndrome, or severe untreated sleep apnea
Second degree atrioventricular (AV) Block , or third degree heart block unless subjects have a pacemaker in place
Prolonged QT corrected for heart rate using Fridericia's formula (QTcF) interval (QTcF > 450 ms males, > 470 ms females)
Resting heart rate (HR) <55 bpm when taking vitals as part of a physical examination at Screening
11. Subject has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c (HbA1c) > 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy
12. Subject has a history of uveitis (within the last year prior to Screening) or clinically confirmed diagnosis of macular edema
13. Subject has a known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease [excluding fungal infection of nail beds, minor upper respiratory tract infections, and minor skin infections]) or any major episode of infection that required hospitalization or treatment with intravenous (IV) antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening
14. History or known presence of recurrent or chronic infection (eg, hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus [HIV]); recurrent urinary tract infections are allowed
15. Subject has a history of active cancer within 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that have been excised and resolved); or colonic
dysplasia that has not been completely removed
16. Subject has a history of alcohol or drug abuse within 1 year prior to initiation of Screening
Exclusions Related to Medications:
17. Hypersensitivity to active ingredients or excipients of ozanimod or placebo
18. Subject has a history of primary nonresponse to 2 or more approved biologic therapies used for the treatment of CD
19. Subject has been treated with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is shorter) prior to the first dose of study drug
20. Subject has a history of treatment with an investigational agent within 5 elimination half-lives of that agent prior to the first dose of study drug
21. Subject has received a live or live attenuated vaccine within 4 weeks prior to the first dose of study drug
22. Subject has received previous treatment with lymphocyte-depleting therapies (eg, Campath®, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, or
daclizumab)
23. Subject has received previous treatment with D-penicillamine, leflunomide, or halidomide
24. Subject has received previous treatment with natalizumab or fingolimod
25. Subject has received previous treatment with oral cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of initiation of Screening
26. Subject has a history of treatment with IV immune globulin (IVIg), or plasmapheresis within 3 months prior to first dose of study drug
27. Subject has discontinued oral or rectal 5-ASA or corticosteroids within 2 weeks prior to the screening endoscopy.
28. Subject has planned concurrent treatment with immunomodulatory agents (eg,azathioprine, 6-MP, cyclosporine, or methotrexate) after randomization. Subjects receivingazathioprine, 6-MP, or methotrexate at screening must discontinue treatment with these agents prior to first dose of study drug
29. Subject has chronic nonsteroidal 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)
30. Subject treated with Class Ia or Class III anti-arrhythmic drugs or with 2 or more agents in combination known to prolong PR interval.
31. Subject receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
32. Subject is receiving treatment with any of the following drugs or interventions within the corresponding timeframe:
- At randomization
o CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) and inducers (eg, rifampicin)
- Two weeks prior to randomization
o Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
Exclusions Related to Laboratory Results:
33. Subject has screening ECG results showing any clinically significant abnormality.
34. Subject has serum creatinine results >1.4 mg/dL for women or > 1.6 mg/dL for men.
35. Subject has liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) results > 2 times the upper limit of normal (ULN), or direct bilirubin > 1.5 times the ULN.
36. Subject has a platelet count < 100,000/μL.
37. Subject has hemoglobin < 7.5 g/dL.
38. Subject has neutrophils < 1500/μL.
39. Subject has an absolute white blood cell (WBC) count <3500/μL.
40. Subject has an absolute lymphocyte count (ANC) < 800 cells/μL.
41. Subject has a forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) <70% of predicted values at screening
The Estimated Number of Participants
-
Taiwan
9 participants
-
Global
600 participants
