Colitis, Ulcerative
Conditions
Keywords
Ulcerative Colitis, Ozanimod, RPC-1063, Zeposia®, Inflammatory bowel disease
Brief summary
The purpose of this study is to explore the safety, efficacy, effects on quality of life (QOL), and biomarker response of ozanimod in participants with moderate to severely active ulcerative colitis (UC) in clinical practice.
Interventions
DRUGOzanimod
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A diagnosis of ulcerative colitis (UC), with signs and symptoms consistent with UC for at least 3 months prior to the first study intervention administration * Moderate to severely active UC disease activity, defined as a modified Mayo score of 4 through 9, inclusive, with the following minimum subscores: i) An SF subscore ≥ 1, AND ii) An RB subscore ≥ 1, AND iii) An ES ≥ 2 (endoscopy performed within 60 days of the first study intervention administration). * Report of a previous colonoscopy that documents extent of disease
Exclusion criteria
* Current or recent (within 3 months of screening) evidence of fulminant colitis, toxic megacolon, or bowel perforation * Extensive colonic resection or current stoma * Colonic dysplasia that has not been removed Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Achieving Clinical Response Measured by Modified Mayo Score for Cohort 2 at Week 26 | At week 26 | Clinical response is defined as meeting all of the following improvements from baseline in the Modified Mayo Score: * Decrease from baseline ≥ 2 points, * Decrease from baseline ≥ 35%, * Decrease from baseline in the Rectal Bleeding (RB) subscore ≥ 1 point or absolute RB subscore ≤ 1 The Modified Mayo Score is a tool that helps doctors measure how active ulcerative colitis is. It combines three components: * Stool Frequency (SF): scored 0-3 (higher score = more frequent stools), * Rectal Bleeding (RB): scored 0-3 (higher score = more bleeding), * Endoscopic Subscore (ES): scored 0-3 (higher score = more severe inflammation seen during endoscopy). The total score ranges from 0 to 9, with higher scores meaning more severe disease activity and lower scores meaning less disease activity and better clinical condition. |
| Percent of Participants Achieving Clinical Response Measured by Modified Mayo Score for Cohort 1 at Week 12 | At week 12 | Clinical response is defined as meeting all of the following improvements from baseline in the Modified Mayo Score: * Decrease from baseline ≥ 2 points, * Decrease from baseline ≥ 35%, * Decrease from baseline in the Rectal Bleeding (RB) subscore ≥ 1 point or absolute RB subscore ≤ 1 The Modified Mayo Score is a tool that helps doctors measure how active ulcerative colitis is. It combines three components: * Stool Frequency (SF): scored 0-3 (higher score = more frequent stools), * Rectal Bleeding (RB): scored 0-3 (higher score = more bleeding), * Endoscopic Subscore (ES): scored 0-3 (higher score = more severe inflammation seen during endoscopy). The total score ranges from 0 to 9, with higher scores meaning more severe disease activity and lower scores meaning less disease activity and better clinical condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) | From first dose of study medication through post-medication follow-up visit (Up to approximately 812 days) | Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, is a congenital anomaly/birth defect, requires in-patient hospitalization or causes prolongation of existing hospitalization, or results in persistent/significant disability/incapacity. Treatment Emergent Serious Adverse Event (TE SAE) is a SAE that meets any of the following: * Starts after the first dose of the study treatment (or within 84 days after stopping it) and was not present before; or * Was already present before treatment but gets worse after the first dose (or within 84 days after stopping it); or * Has missing onset and end dates, making it unclear whether it occurred outside the treatment-emergent period. Participants meeting any of these conditions are counted as having at least one TESAE. |
| Number of Participants With Treatment Emergent Adverse Event of Interest | From first dose of study medication through post-medication follow-up visit (Up to approximately 812 days) | This endpoint reports the number of participants who experienced Adverse Events of Interest (AEIs) during the study. AEIs include bradycardia, heart conduction abnormalities (second-degree and higher atrioventricular block), macular edema, malignancy, serious or opportunistic infection, pulmonary effects, hepatic effects, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy (PML), and events associated with orthostatic hypotension (e.g., dizziness, lightheadedness, syncope, seizure). The Sponsor may request additional information for nonserious AEIs. A Treatment Emergent AEI is an AEI that starts after the first dose (or within 84 days after stopping), worsens relative to baseline in this period (or within 84 days after stopping), or has missing dates making the timing unclear. Participants meeting any of these conditions are counted as having at least one AEI. |
| Number of Participants With Treatment Emergent Adverse Events Leading to Discontinuation | From first dose of study medication through post-medication follow-up visit (Up to approximately 812 days) | This endpoint measures the number of participants who experienced Treatment Emergent Adverse Events (TEAEs) that resulted in discontinuation of study treatment. An Adverse Event (AE) is any new medical problem or worsening of a preexisting condition in a study participant who receives the study treatment. It does not have to be caused by the treatment. An AE can be any unfavorable and unintended sign (such as an abnormal lab finding), symptom, or disease that happens around the time the study treatment is used, whether or not it is related to the treatment. A TEAE is an AE that: starts after the first dose (or within 84 days after stopping) and was not present before; or was preexisting but worsens after the first dose (or within 84 days after stopping); or has missing dates that prevent determining whether it occurred outside the treatment emergent period. |
| Number of Participants With Clinically Significant Changes in Laboratory Assessments | From first dose of study medication through end of study (Up to approximately 728 days) | Number of participants experiencing clinically significant abnormalities in laboratory testing including hematology, chemistry and urinalysis. |
| Percent of Participants Achieving Clinical Remission by Partial Mayo Score at Week 52 and 104 | At week 52 and week 104 | Clinical remission is defined as a Partial Mayo Score of ≤ 2.5. The Partial Mayo Score is a tool that helps doctors measure how active ulcerative colitis is without using endoscopy. It combines three components: * Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools) * Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding) * Physician's Global Assessment (PGA): range 0-3 (higher score = worse overall condition based on physician's judgment) The total score ranges from 0 to 9, with lower scores meaning fewer symptoms and better disease control, and higher scores meaning more severe disease activity. A score of 2.5 or below suggests the disease is in remission. |
| Percent of Participants Achieving Corticosteroid-free Clinical Remission by Partial Mayo Score at Week 52 and 104 | At week 52 and week 104 | Corticosteroid-free Clinical Remission (Partial Mayo Score) is defined as: * Meeting the criteria for clinical remission by Partial Mayo Score \<=2.5, and * No use of oral systemic corticosteroids in the prior 90 days. The Partial Mayo Score is a tool that helps doctors measure ulcerative colitis activity without endoscopy. It combines three components: * Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools) * Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding) * Physician's Global Assessment (PGA): range 0-3 (higher score = worse overall condition based on physician's judgment) The total score ranges from 0 to 9, with lower scores meaning fewer symptoms and better disease control, and higher scores meaning more severe disease activity |
| Percent of Participants Achieving Clinical Response by Partial Mayo Score at Week 52 and 104 | At week 52 and week 104 | Clinical Response by Partial Mayo Score is defined as: * Decrease in partial Mayo score ⩾ 2 points and ⩾ 30% from baseline, and * Decrease in rectal bleeding subscore \> 1 point or absolute rectal bleeding score \< 1 This represents a marked improvement in disease activity. The Partial Mayo Score is a tool that helps doctors measure ulcerative colitis activity without endoscopy. It combines three components: * Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools) * Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding) * Physician's Global Assessment (PGA): range 0-3 (higher score = worse overall condition based on physician's judgment) The total score ranges from 0 to 9, with lower scores meaning fewer symptoms and better disease control, and higher scores meaning more severe disease activity. |
| Percent of Participants Achieving Clinical Remission Measured by Modified Mayo Score for Cohort 1 at Week 12 | At week 12 | Clinical remission by Modified Mayo Score is defined as meeting all of the following criteria: * Stool Frequency (SF) subscore ≤ 1, with at least a 1-point decrease from baseline * Rectal Bleeding (RB) subscore = 0 * Endoscopic Subscore (ES) ≤ 1 The Modified Mayo Score is the sum of the following components (Range: 0-9): * SF subscore: range 0-3 (higher score = more frequent stools) * RB subscore: range 0-3 (higher score = more bleeding) * ES: range 0-3 (higher score = more severe inflammation seen during endoscopy) The total score ranges from 0 to 9, with lower scores meaning less disease activity and better clinical condition, and higher scores meaning more severe disease activity. |
| Percent of Participants Achieving Endoscopic Response for Cohort 1 at Week 12 | At week 12 | Endoscopic Response is defined as: • A decrease from baseline of ≥ 1 point in the Mayo Endoscopic Score (ES). Mayo Endoscopic Score: range 0-3 * Higher ES scores = more severe inflammation and worse mucosal appearance * Lower ES scores = less inflammation and better mucosal healing |
| Percent of Participants Achieving Endoscopic Improvement for Cohort 1 at Week 12 | At week 12 | Endoscopic Improvement is defined as: • Mayo Endoscopic Score (ES) ≤ 1 Mayo Endoscopic Score (ES): range 0-3 * Higher ES scores = more severe inflammation and worse mucosal appearance * Lower ES scores = less inflammation and better mucosal healing |
| Percent of Participants Achieving Histological Improvement for Cohort 1 at Week 12 | At week 12 | Histological Improvement is defined as: • Achieving a Geboes score \< 3.1 The Geboes score is a grading system used to assess inflammation in tissue samples under a microscope. * Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity. * Higher Geboes scores = more severe microscopic inflammation * Lower Geboes scores = less inflammation and better healing |
| Change in the Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score From Baseline to Week 12 for Cohort 1 | At baseline and week 12 | IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis \[UC\] and Crohn's Disease \[CD\]). It includes 32 questions across 4 dimensions: * Bowel symptoms (10 items) * Systemic symptoms (5 items) * Emotional function (12 items) * Social function (5 items) Scoring: Each question ranges from 1 ("worst") to 7 ("best"). Total score: 32-224, with higher scores indicating better quality of life (QOL). An increase from baseline reflects improved health-related quality of life (HRQOL). The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall HRQOL. |
| Percent of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Response [Change in Total Score (≥16 Points) From Baseline to Week 12] for Cohort 1 | At baseline and week 12 | IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis \[UC\] and Crohn's Disease \[CD\]). It includes 32 questions across 4 dimensions: * Bowel symptoms: 10 items * Systemic symptoms: 5 items * Emotional function: 12 items * Social function: 5 items Scoring: * Each question ranges from 1 ("worst") to 7 ("best"). * Total score: 32-224, with higher scores indicating better quality of life (QOL). A change from baseline in total score of ≥16 points reflect meaningful IBDQ response. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL). |
| Percent of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission [Total Score (≥170 Points)] for Cohort 1 at Week 12 | At week 12 | IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis \[UC\] and Crohn's Disease \[CD\]). It includes 32 questions across 4 dimensions: * Bowel symptoms: 10 items * Systemic symptoms: 5 items * Emotional function: 12 items * Social function: 5 items Scoring: * Each question ranges from 1 ("worst") to 7 ("best"). * Total score: 32-224, with higher scores indicating better quality of life (QOL). A total score of ≥170 points reflects IBDQ remission, meaning the participant reports very few symptoms and good overall quality of life. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL). |
| Percent of Participants Achieving Clinical Remission Measured by Modified Mayo Score for Cohort 2 at Week 26 | At week 26 | Clinical remission by Modified Mayo Score is defined as meeting all of the following criteria: * Stool Frequency (SF) subscore ≤ 1, with at least a 1-point decrease from baseline * Rectal Bleeding (RB) subscore = 0 * Endoscopic Subscore (ES) ≤ 1 The Modified Mayo Score is the sum of the following components (Range: 0-9): * SF subscore: range 0-3 (higher score = more frequent stools) * RB subscore: range 0-3 (higher score = more bleeding) * ES: range 0-3 (higher score = more severe inflammation seen during endoscopy) The total score ranges from 0 to 9, with lower scores meaning less disease activity and better clinical condition, and higher scores meaning more severe disease activity. |
| Percent of Participants Achieving Endoscopic Response for Cohort 2 at Week 26 | At week 26 | Endoscopic Response is defined as: • A decrease from baseline of ≥ 1 point in the Mayo Endoscopic Sub score (ES). This represents the percentage of treated participants who achieved a decrease from baseline of at least 1 point in the Mayo ES, indicating improvement in mucosal appearance during endoscopy. Mayo Endoscopic Subscore (ES): range 0-3 * Higher ES scores = more severe inflammation and worse mucosal appearance * Lower ES scores = less inflammation and better mucosal healing |
| Percent of Participants Achieving Endoscopic Remission for Cohort 2 at Week 26 | At week 26 | Endoscopic Remission is defined as: • Mayo Endoscopic Sub score (ES) = 0 This represents the percentage of treated participants with Mayo ES = 0, indicating complete mucosal healing. Mayo Endoscopic Sub score (ES): range 0-3 * Higher ES scores = more severe inflammation and worse mucosal appearance * Lower ES scores = less inflammation and better mucosal healing |
| Percent of Participants Achieving Histological Improvement for Cohort 2 at Week 26 | At week 26 | Histological Improvement is defined as: • Achieving a Geboes score \< 3.1 The Geboes score is a grading system used to assess inflammation in tissue samples under a microscope. * Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity. * Higher Geboes scores = more severe microscopic inflammation * Lower Geboes scores = less inflammation and better healing |
| Percent of Participants Achieving Histological Remission for Cohort 2 at Week 26 | At week 26 | Histological Remission is defined as: • Achieving a Geboes score \< 2 The Geboes score is a grading system used to assess inflammation in tissue samples under a microscope. * Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity. * Higher Geboes scores = more severe microscopic inflammation * Lower Geboes scores = minimal or no inflammation and better healing |
| Change in the Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score From Baseline to Week 26 for Cohort 2 | At baseline and week 26 | IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis \[UC\] and Crohn's Disease \[CD\]). It includes 32 questions across 4 dimensions: * Bowel symptoms (10 items) * Systemic symptoms (5 items) * Emotional function (12 items) * Social function (5 items) Scoring: Each question ranges from 1 ("worst") to 7 ("best"). Total score: 32-224, with higher scores indicating better quality of life (QOL). An increase from baseline reflects improved health-related quality of life (HRQOL). The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall HRQOL. |
| Percent of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Response [Change in Total Score (≥16 Points) From Baseline to Week 26] for Cohort 2 | At baseline and week 26 | IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis \[UC\] and Crohn's Disease \[CD\]). It includes 32 questions across 4 dimensions: * Bowel symptoms: 10 items * Systemic symptoms: 5 items * Emotional function: 12 items * Social function: 5 items Scoring: * Each question ranges from 1 ("worst") to 7 ("best"). * Total score: 32-224, with higher scores indicating better quality of life (QOL). A change from baseline in total score of ≥16 points reflect meaningful IBDQ response. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL). |
| Percent of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission [Total Score (≥170 Points)] for Cohort 2 at Week 26 | At week 26 | IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis \[UC\] and Crohn's Disease \[CD\]). It includes 32 questions across 4 dimensions: * Bowel symptoms: 10 items * Systemic symptoms: 5 items * Emotional function: 12 items * Social function: 5 items Scoring: * Each question ranges from 1 ("worst") to 7 ("best"). * Total score: 32-224, with higher scores indicating better quality of life (QOL). A total score of ≥170 points reflect IBDQ remission, meaning the participant reports very few symptoms and good overall quality of life. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL). |
| Percent of Participants Achieving Corticosteroid-free Clinical Remission by Modified Mayo Score for Cohort 2 at Week 26 | At week 26 | Corticosteroid-free Clinical Remission (modified mayo score) is defined as: * Meeting the criteria for clinical remission by Modified Mayo Score \[Stool Frequency (SF) subscore ≤ 1, with ≥ 1 point decrease from baseline and; Rectal Bleeding (RB) subscore = 0 and; Endoscopic Subscore (ES) ≤ 1\], and * No oral systemic steroid use in the prior 90 days. The Modified Mayo Score is the sum of the following components (Range: 0-9): * Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools) * Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding) * Endoscopic Subscore (ES): range 0-3 (higher score = more severe inflammation seen during endoscopy) The total score ranges from 0 to 9, with: * Lower scores = less disease activity and better clinical condition * Higher scores = more severe disease activity |
| Percent of Participants Achieving Endoscopic Improvement for Cohort 2 at Week 26 | At week 26 | Endoscopic Improvement is defined as: • Mayo Endoscopic Subscore (ES) ≤ 1 This represents the percentage of treated participants with Mayo ES ≤ 1, indicating mild or no inflammation. Mayo Endoscopic Subscore (ES): range 0-3 * Higher ES scores = more severe inflammation and worse mucosal appearance * Lower ES scores = less inflammation and better mucosal healing |
| Percent of Participants Achieving Histo-endoscopic Mucosal Improvement (HEMI) for Cohort 2 at Week 26 | At week 26 | Histo-endoscopic Mucosal Improvement (HEMI) is defined as: * Mayo Endoscopic Subscore (ES) ≤ 1, and * Geboes score \< 3.1 Mayo Endoscopic Subscore (ES): range 0-3 * Higher ES scores = more severe visible inflammation and worse mucosal appearance * Lower ES scores = less visible inflammation and better mucosal healing Geboes Score: * Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity * Higher Geboes scores = more severe microscopic inflammation * Lower Geboes scores = less microscopic inflammation and better tissue healing Meeting both criteria (ES ≤ 1 and Geboes \< 3.1) shows improvement in both endoscopic appearance and microscopic tissue health. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose of study medication through post-medication follow-up visit (Up to approximately 812 days) | An Adverse Event (AE) is any new medical problem or worsening of a preexisting condition in a study participant who receives the study treatment. It does not have to be caused by the treatment. An AE can be any unfavorable and unintended sign (such as an abnormal lab finding), symptom, or disease that happens around the time the study treatment is used, whether or not it is related to the treatment. A Treatment Emergent Adverse Event (TEAE) is an AE that meets any of the following: * Starts after the first dose of the study treatment (or within 84 days after stopping it) and was not present before; or * Was already present before treatment but gets worse after the first dose (or within 84 days after stopping it); or * Has missing onset and end dates, making it unclear whether it occurred outside the treatment-emergent period. Participants meeting any of these conditions are counted as having at least one TEAE. |
Countries
United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
Total 139 participants were enrolled and treated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.9 Years STANDARD_DEVIATION 15.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 109 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 99 | 0 / 40 |
| other Total, other adverse events | 28 / 99 | 9 / 40 |
| serious Total, serious adverse events | 7 / 99 | 4 / 40 |
Outcome results
None listed