Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to determine whether RPC1063 is effective in the treatment of Ulcerative Colitis (UC).
Detailed description
The trial is composed of 2 periods: Induction and Maintenance. In the Induction Period (IP), patients will be entered into the trial in 2 separate cohorts (Cohort 1 and Cohort 2).Patients from Cohort 1 and 2 in clinical response at the end of the IP will proceed through to the Maintenance Period (MP). Patients from Cohort 1 and 2 who participate in this trial may also qualify to participate in an optional Open-Label Extension (OLE) trial.
Interventions
DRUGRPC1063
DRUGPlacebo
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 75 years (at screening for Cohort 1 and 2) * UC confirmed on endoscopy * Moderately to severely active UC (May score 6-12) * Currently receiving treatment with aminosalisylate, prednisone, or budesonide * Can be receiving azathioprine, mercaptopurine, or methotrexate, but treatment will be stopped prior to randomization
Exclusion criteria
* Have severe extensive colitis as evidence by: * Physician judgment that the patient is likely to require colectomy or ileostomy within 12 weeks of baseline. * Current or recent (within 3 months) evidence of fulminant colitis, toxic megacolon, or bowel perforation. * Diagnosis of CD, indeterminate colitis, or the presence of fistula consistent with CD or microscopic colitis, radiation colitis, or ischemic colitis * Clinically relevant cardiovascular conditions or other relevant diseases that could impact the implementation or interpretation of the trial, or put the patient at risk * History of uveitis or unknown macular edema * Pregnancy, lactation, or a positive serum β-human chorionic gonadotropin (β-hCG) measured during screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Clinical Remission at 10 Weeks | At 10 Weeks | Percentage of participants that are in Clinical remission at 10 weeks |
| Percentage of Participants in Clinical Remission at 52 Weeks | At 52 Weeks | Percentage of participants that are in Clinical remission at 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response at 10 Weeks | At 10 Weeks | Percentage of participants that are in Clinical response at 10 weeks |
| Percentage of Participants With Endoscopic Improvement at 10 Weeks | At 10 Weeks | Percentage of participants with endoscopic improvement at 10 weeks |
| Percentage of Participants With Mucosal Healing at 10 Weeks | At 10 Weeks | Percentage of participants with mucosal healing at 10 weeks |
| Percentage of Participants in Clinical Response at 52 Weeks | At 52 Weeks | Percentage of participants that are in Clinical response at 52 weeks |
| Percentage of Participants With Endoscopic Improvement at 52 Weeks | At 52 Weeks | Percentage of participants with endoscopic improvement at 52 weeks |
| Percentage of Participants in Clinical Remission at Week 52 Who Were in Remission at Week 10 | At 52 Weeks | Percentage of participants in clinical remission at week 52 who were in clinical remission at week 10 |
| Percentage of Participants With Corticosteroid Free Remission at 52 Weeks | At 52 Weeks | Percentage of participants with corticosteroid free remission at 52 weeks |
| Percentage of Participants With Mucosal Healing at 52 Weeks | At 52 Weeks | Percentage of participants with Mucosal Healing at 52 weeks |
| Percentage of Participants With Durable Clinical Remission at 52 Weeks | At 52 Weeks | Percentage of participants with durable clinical remission at 52 weeks |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Croatia, Czechia, Georgia, Germany, Greece, Hungary, Israel, Italy, Latvia, Moldova, Netherlands, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
1012 Participants randomized and treated
Participants by arm
| Arm | Count |
|---|---|
| RPC1063 Cohort 1(Induction Period) * Blinded
* On Days 1 to 4, RPC1063/ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg) once daily (one 0.25 mg capsule)
* On Days 5 to 7, RPC1063/ozanimod HCl 0.5 mg (equivalent to ozanimod 0.46 mg) once daily (two 0.25 mg capsules)
* On Day 8, patients will receive the final dose RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) once daily for 9 weeks (one 1 mg capsule) | 429 |
| Placebo Cohort 1 (Induction Period) -Blinded Placebo Participants started in induction period and some continued to receive placebo in the Maintenance Period in a double blind manner. | 216 |
| RPC1063 Cohort 2 (Induction Period) * Open Label
* On Days 1 to 4, RPC1063/ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg) or matching placebo once daily (one 0.25 mg capsule)
* On Days 5 to 7, RPC1063/ozanimod HCl 0.5 mg (equivalent to ozanimod 0.46 mg) or matching placebo once daily (two 0.25 mg capsules)
* On Day 8, patients will receive the final dose RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) or matching placebo once daily for 9 weeks (one 1 mg capsule) | 367 |
| RPC1063 (Maintenance Period) \- Blinded RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) once daily for 42 weeks (one 1 mg capsule) | 230 |
| Placebo (Maintenance Period) \- Blinded Placebo | 227 |
| Total | 1,469 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 6 | 12 | 0 | 0 |
| Overall Study | Lack of Efficacy | 4 | 10 | 9 | 0 | 0 |
| Overall Study | non compliance with protocol | 2 | 0 | 1 | 0 | 0 |
| Overall Study | Other Reason | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 8 | 20 | 0 | 0 |
Baseline characteristics
| Characteristic | RPC1063 Cohort 1(Induction Period) | Placebo Cohort 1 (Induction Period) | RPC1063 Cohort 2 (Induction Period) | Total | Placebo (Maintenance Period) | RPC1063 (Maintenance Period) |
|---|---|---|---|---|---|---|
| Age, Categorical Induction Period <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — |
| Age, Categorical Induction Period >=65 years | 19 Participants | 14 Participants | 21 Participants | 54 Participants | — | — |
| Age, Categorical Induction Period Between 18 and 65 years | 410 Participants | 202 Participants | 346 Participants | 958 Participants | — | — |
| Age, Categorical Maintenance Period <=18 years | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Maintenance Period >=65 years | — | — | — | 25 Participants | 12 Participants | 13 Participants |
| Age, Categorical Maintenance Period Between 18 and 65 years | — | — | — | 432 Participants | 215 Participants | 217 Participants |
| Ethnicity (NIH/OMB) Induction Period Hispanic or Latino | 26 Participants | 8 Participants | 16 Participants | 50 Participants | — | — |
| Ethnicity (NIH/OMB) Induction Period Not Hispanic or Latino | 403 Participants | 208 Participants | 351 Participants | 962 Participants | — | — |
| Ethnicity (NIH/OMB) Induction Period Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — |
| Ethnicity (NIH/OMB) Maintenance Period Hispanic or Latino | — | — | — | 22 Participants | 13 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Maintenance Period Not Hispanic or Latino | — | — | — | 435 Participants | 214 Participants | 221 Participants |
| Ethnicity (NIH/OMB) Maintenance Period Unknown or Not Reported | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Induction Period American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Induction Period Asian | 36 Participants | 17 Participants | 12 Participants | 65 Participants | — | — |
| Race (NIH/OMB) Induction Period Black or African American | 14 Participants | 4 Participants | 10 Participants | 28 Participants | — | — |
| Race (NIH/OMB) Induction Period More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Induction Period Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Induction Period Unknown or Not Reported | 9 Participants | 3 Participants | 9 Participants | 21 Participants | — | — |
| Race (NIH/OMB) Induction Period White | 370 Participants | 192 Participants | 336 Participants | 898 Participants | — | — |
| Race (NIH/OMB) Maintenance Period American Indian or Alaska Native | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Maintenance Period Asian | — | — | — | 25 Participants | 12 Participants | 13 Participants |
| Race (NIH/OMB) Maintenance Period Black or African American | — | — | — | 18 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) Maintenance Period More than one race | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Maintenance Period Native Hawaiian or Other Pacific Islander | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Maintenance Period Unknown or Not Reported | — | — | — | 7 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Maintenance Period White | — | — | — | 407 Participants | 202 Participants | 205 Participants |
| Sex: Female, Male Induction Period Female | 184 Participants | 73 Participants | 153 Participants | 410 Participants | — | — |
| Sex: Female, Male Induction Period Male | 245 Participants | 143 Participants | 214 Participants | 602 Participants | — | — |
| Sex: Female, Male Maintenance Period Female | — | — | — | 239 Participants | 122 Participants | 117 Participants |
| Sex: Female, Male Maintenance Period Male | — | — | — | 218 Participants | 105 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 429 | 0 / 216 | 1 / 367 | 0 / 230 | 0 / 227 |
| other Total, other adverse events | 15 / 429 | 13 / 216 | 15 / 367 | 2 / 230 | 4 / 227 |
| serious Total, serious adverse events | 17 / 429 | 11 / 216 | 23 / 367 | 12 / 230 | 18 / 227 |
Outcome results
Primary
Percentage of Participants in Clinical Remission at 10 Weeks
Percentage of participants that are in Clinical remission at 10 weeks
Time frame: At 10 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RPC1063 Cohort 1(Induction Period) | Percentage of Participants in Clinical Remission at 10 Weeks | 18.4 Percentage |
| Placebo Cohort 1 (Induction Period) | Percentage of Participants in Clinical Remission at 10 Weeks | 6.0 Percentage |
| RPC1063 Cohort 2 (Induction Period) | Percentage of Participants in Clinical Remission at 10 Weeks | 21.0 Percentage |
p-value: 0.000195% CI: [1.938, 6.636]Cochran-Mantel-Haenszel
Primary
Percentage of Participants in Clinical Remission at 52 Weeks
Percentage of participants that are in Clinical remission at 52 weeks
Time frame: At 52 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants in Clinical Remission at 52 Weeks | 24.6 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants in Clinical Remission at 52 Weeks | 37.0 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants in Clinical Remission at 52 Weeks | 18.5 Percentage |
p-value: 0.000195% CI: [1.767, 4.294]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Clinical Remission at Week 52 Who Were in Remission at Week 10
Percentage of participants in clinical remission at week 52 who were in clinical remission at week 10
Time frame: At 52 Weeks
Population: ITT Population who were in remission at week 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants in Clinical Remission at Week 52 Who Were in Remission at Week 10 | 41.7 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants in Clinical Remission at Week 52 Who Were in Remission at Week 10 | 51.9 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants in Clinical Remission at Week 52 Who Were in Remission at Week 10 | 29.3 Percentage |
Secondary
Percentage of Participants in Clinical Response at 52 Weeks
Percentage of participants that are in Clinical response at 52 weeks
Time frame: At 52 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants in Clinical Response at 52 Weeks | 39.1 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants in Clinical Response at 52 Weeks | 60.0 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants in Clinical Response at 52 Weeks | 41.0 Percentage |
Secondary
Percentage of Participants With Clinical Response at 10 Weeks
Percentage of participants that are in Clinical response at 10 weeks
Time frame: At 10 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RPC1063 Cohort 1(Induction Period) | Percentage of Participants With Clinical Response at 10 Weeks | 47.8 Percentage |
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Clinical Response at 10 Weeks | 25.9 Percentage |
| RPC1063 Cohort 2 (Induction Period) | Percentage of Participants With Clinical Response at 10 Weeks | 52.6 Percentage |
Secondary
Percentage of Participants With Corticosteroid Free Remission at 52 Weeks
Percentage of participants with corticosteroid free remission at 52 weeks
Time frame: At 52 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Corticosteroid Free Remission at 52 Weeks | 24.6 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants With Corticosteroid Free Remission at 52 Weeks | 31.7 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants With Corticosteroid Free Remission at 52 Weeks | 16.7 Percentage |
Secondary
Percentage of Participants With Durable Clinical Remission at 52 Weeks
Percentage of participants with durable clinical remission at 52 weeks
Time frame: At 52 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Durable Clinical Remission at 52 Weeks | 7.2 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants With Durable Clinical Remission at 52 Weeks | 17.8 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants With Durable Clinical Remission at 52 Weeks | 9.7 Percentage |
Secondary
Percentage of Participants With Endoscopic Improvement at 10 Weeks
Percentage of participants with endoscopic improvement at 10 weeks
Time frame: At 10 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RPC1063 Cohort 1(Induction Period) | Percentage of Participants With Endoscopic Improvement at 10 Weeks | 27.3 Percentage |
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Endoscopic Improvement at 10 Weeks | 11.6 Percentage |
| RPC1063 Cohort 2 (Induction Period) | Percentage of Participants With Endoscopic Improvement at 10 Weeks | 27.2 Percentage |
Secondary
Percentage of Participants With Endoscopic Improvement at 52 Weeks
Percentage of participants with endoscopic improvement at 52 weeks
Time frame: At 52 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Endoscopic Improvement at 52 Weeks | 29.0 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants With Endoscopic Improvement at 52 Weeks | 45.7 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants With Endoscopic Improvement at 52 Weeks | 26.4 Percentage |
Secondary
Percentage of Participants With Mucosal Healing at 10 Weeks
Percentage of participants with mucosal healing at 10 weeks
Time frame: At 10 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RPC1063 Cohort 1(Induction Period) | Percentage of Participants With Mucosal Healing at 10 Weeks | 12.6 Percentage |
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Mucosal Healing at 10 Weeks | 3.7 Percentage |
| RPC1063 Cohort 2 (Induction Period) | Percentage of Participants With Mucosal Healing at 10 Weeks | 11.4 Percentage |
Secondary
Percentage of Participants With Mucosal Healing at 52 Weeks
Percentage of participants with Mucosal Healing at 52 weeks
Time frame: At 52 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Cohort 1 (Induction Period) | Percentage of Participants With Mucosal Healing at 52 Weeks | 10.1 Percentage |
| RPC1063 (Maintenance Period) | Percentage of Participants With Mucosal Healing at 52 Weeks | 29.6 Percentage |
| Placebo (Maintenance Period) | Percentage of Participants With Mucosal Healing at 52 Weeks | 14.1 Percentage |