Clinical Trials List
Protocol NumberRPC01-3203
NCT Number(ClinicalTrials.gov Identfier)NCT03464097
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
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease
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Trial Applicant
TAIWAN PSI HEALTH DEVELOPMENT COMPANY LIMITED
-
Sponsor
Celgene International II Sàrl
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Trial scale
Multi-Regional Multi-Center
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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
- Yu-Chung Su Digestive System Department
- I-CHEN WU 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
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
- 林偉彬 Digestive System Department
- Cheng-Yu Lin Digestive System Department
- 許振銘 Digestive System Department
- Chia-Jung Kuo Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Crohn’s disease, CD
Objectives
This is a Phase 3, randomized, double-blind, placebo-controlled study to demonstrate the effect of oral ozanimod as maintenance therapy in adult and adolescent subjects with moderately to severely active CD, defined as a CDAI score of ≥ 220 to ≤ 450.
Test Drug
Ozanimod
Active Ingredient
RPC1063
Dosage Form
capsule
Dosage
0.25, 1
Endpoints
Primary Objective:
• Demonstrate the efficacy of ozanimod compared to placebo on the maintenance of
clinical remission and endoscopic response
Secondary Objectives:
• Demonstrate the efficacy of ozanimod compared to placebo on maintenance of clinical response
• Demonstrate the efficacy of ozanimod compared to placebo on maintenance of endoscopic remission and mucosal healing
• Demonstrate the efficacy of ozanimod, compared to placebo, in achieving corticosteroid-free remission among subjects receiving corticosteroids at entry into the Maintenance Study
• Demonstrate the efficacy of ozanimod, compared to placebo, on maintenance of
clinical remission in adolescent subjects with active CD
• Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD)
relationship of ozanimod
• Demonstrate the efficacy of ozanimod, compared to placebo, on healthcare resource
utilization (HRU), subject-reported outcomes, and quality of life
• Demonstrate the safety and tolerability of ozanimod as maintenance therapy
• Demonstrate the efficacy of ozanimod compared to placebo on the maintenance of
clinical remission and endoscopic response
Secondary Objectives:
• Demonstrate the efficacy of ozanimod compared to placebo on maintenance of clinical response
• Demonstrate the efficacy of ozanimod compared to placebo on maintenance of endoscopic remission and mucosal healing
• Demonstrate the efficacy of ozanimod, compared to placebo, in achieving corticosteroid-free remission among subjects receiving corticosteroids at entry into the Maintenance Study
• Demonstrate the efficacy of ozanimod, compared to placebo, on maintenance of
clinical remission in adolescent subjects with active CD
• Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD)
relationship of ozanimod
• Demonstrate the efficacy of ozanimod, compared to placebo, on healthcare resource
utilization (HRU), subject-reported outcomes, and quality of life
• Demonstrate the safety and tolerability of ozanimod as maintenance therapy
Inclution Criteria
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject fulfilled the inclusion criteria at time of entry into the Induction Study (RPC01-3201 or RPC01-3202) and have completed the Week 12 efficacy assessments of the Induction Study.
4. Subject is in clinical response (a reduction from baseline in CDAI of ≥ 100 points or CDAI score of < 150 points) and/or in clinical remission based on an average daily stool frequency score ≤ 3 with abdominal pain and stool frequency no worse than
baseline and an average abdominal pain score ≤ 1 and/or CDAI score of < 150 points at Week 12 of the Induction Study.
5. (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. Must be male or female subject aged 18 to 75 years (at Randomization), inclusive. (per-regulation, in Taiwan this study is open to patients aged 20-75 only)
3. Subject must provide written informed consent prior to any study-related procedures and have the ability to comply with the Table of Events
(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.
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject fulfilled the inclusion criteria at time of entry into the Induction Study (RPC01-3201 or RPC01-3202) and have completed the Week 12 efficacy assessments of the Induction Study.
4. Subject is in clinical response (a reduction from baseline in CDAI of ≥ 100 points or CDAI score of < 150 points) and/or in clinical remission based on an average daily stool frequency score ≤ 3 with abdominal pain and stool frequency no worse than
baseline and an average abdominal pain score ≤ 1 and/or CDAI score of < 150 points at Week 12 of the Induction Study.
5. (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. Must be male or female subject aged 18 to 75 years (at Randomization), inclusive. (per-regulation, in Taiwan this study is open to patients aged 20-75 only)
3. Subject must provide written informed consent prior to any study-related procedures and have the ability to comply with the Table of Events
(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.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
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 (β-hCG) measured prior to randomization.
3. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not
been appropriately treated.
4. Subject has a history of uveitis (within the last year) or clinically confirmed diagnosis of
macular edema.
5. Subject has undergone a colectomy (partial or total), small bowel resection, or an ostomy (ie,
temporary colostomy, permanent colostomy, ileostomy, or other enterostomy) since Day 1 of
the Induction Studies or has developed symptomatic fistula (enterocutaneous or
entero-enteral).
6. Subject has had 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.
Exclusions Related to Medications:
7. Hypersensitivity to active ingredients or excipients of ozanimod or placebo
8. Subject has received any of the following therapies during the Induction Study:
a. rectal steroid therapy (ie, steroids administered to the rectum or sigmoid via
foam or enema)
b. rectal 5-ASA (ie, 5-ASA administered to the rectum)
c. parenteral corticosteroids
d. total parenteral nutrition therapy
e. antibiotics for the treatment of CD
f. immunomodulatory agents (6-MP, azathioprine, including but not limited
to cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus)
g. immunomodulatory biologic agents
h. investigational agents
i. apheresis
9. Subject has current or planned treatment with immunomodulatory agents
(eg, azathioprine, 6-MP, or methotrexate) during the Maintenance Study.
10. 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).
11. Subject has received treatment with Class Ia or Class III anti-arrhythmic drugs
or treatment with 2 or more agents in combination known to prolong PR
interval.
12. Subject has received a live or live attenuated vaccine within 4 weeks prior to first dose
of IP.
13. 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).
14. Subject has received previous treatment with D-penicillamine, leflunomide
or thalidomide.
15. Subject has received previous treatment with natalizumab or fingolimod.
16. Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus,
or mycophenolate mofetil within 16 weeks of first dose of IP.
17. Subject has a history of treatment with IV immune globulin (IVIg), or
plasmapheresis, within 3 months prior to first dose of IP.
18. Subject receiving treatment with breast cancer resistance protein (BCRP) inhibitors
(eg, cyclosporine, eltrombopag)
19. Subjects is receiving treatment with any of the following drugs or interventions
within the 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:
20. Subject has ECG results showing any clinically significant abnormality at Week 12 of
the Induction Study.
21. Subject has confirmed aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) > 5 times the ULN
22. Subject has a forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC)
< 50% of predicted values prior to randomization.
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 (β-hCG) measured prior to randomization.
3. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not
been appropriately treated.
4. Subject has a history of uveitis (within the last year) or clinically confirmed diagnosis of
macular edema.
5. Subject has undergone a colectomy (partial or total), small bowel resection, or an ostomy (ie,
temporary colostomy, permanent colostomy, ileostomy, or other enterostomy) since Day 1 of
the Induction Studies or has developed symptomatic fistula (enterocutaneous or
entero-enteral).
6. Subject has had 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.
Exclusions Related to Medications:
7. Hypersensitivity to active ingredients or excipients of ozanimod or placebo
8. Subject has received any of the following therapies during the Induction Study:
a. rectal steroid therapy (ie, steroids administered to the rectum or sigmoid via
foam or enema)
b. rectal 5-ASA (ie, 5-ASA administered to the rectum)
c. parenteral corticosteroids
d. total parenteral nutrition therapy
e. antibiotics for the treatment of CD
f. immunomodulatory agents (6-MP, azathioprine, including but not limited
to cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus)
g. immunomodulatory biologic agents
h. investigational agents
i. apheresis
9. Subject has current or planned treatment with immunomodulatory agents
(eg, azathioprine, 6-MP, or methotrexate) during the Maintenance Study.
10. 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).
11. Subject has received treatment with Class Ia or Class III anti-arrhythmic drugs
or treatment with 2 or more agents in combination known to prolong PR
interval.
12. Subject has received a live or live attenuated vaccine within 4 weeks prior to first dose
of IP.
13. 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).
14. Subject has received previous treatment with D-penicillamine, leflunomide
or thalidomide.
15. Subject has received previous treatment with natalizumab or fingolimod.
16. Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus,
or mycophenolate mofetil within 16 weeks of first dose of IP.
17. Subject has a history of treatment with IV immune globulin (IVIg), or
plasmapheresis, within 3 months prior to first dose of IP.
18. Subject receiving treatment with breast cancer resistance protein (BCRP) inhibitors
(eg, cyclosporine, eltrombopag)
19. Subjects is receiving treatment with any of the following drugs or interventions
within the 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:
20. Subject has ECG results showing any clinically significant abnormality at Week 12 of
the Induction Study.
21. Subject has confirmed aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) > 5 times the ULN
22. Subject has a forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC)
< 50% of predicted values prior to randomization.
The Estimated Number of Participants
-
Taiwan
9 participants
-
Global
485 participants
