Ulcerative Colitis
Conditions
Keywords
Inflammatory Bowel Disease, Gastrointestinal Disease, Ulcerative Colitis, Colitis
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of vixarelimab compared with placebo in participants with moderate to severe UC who have demonstrated inadequate response to, loss of response to, or intolerance to prior conventional or advanced therapy.
Detailed description
This study consists of two periods: 1. An induction period which will test the induction of clinical remission; 2. An optional active treatment extension (ATE) period which will explore durability of clinical response and remission in which all participants will receive vixarelimab.
Interventions
DRUGVixarelimab
Vixarelimab will be administered as per the schedule specified in the respective arms.
DRUGPlacebo
Vixarelimab matching placebo will be administered as per the schedule specified in the respective arms.
Sponsors
Genentech, Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of UC for at least 3 months * Moderately to severely active UC, assessed by mMS * Inadequate response, loss of response to, or intolerance to conventional or advanced therapies for UC
Exclusion criteria
* Diagnosis of Crohn's disease or indeterminate colitis * Suspicion of ischemic, radiation, microscopic, or infectious colitis * Prior colectomy * Inadequate response or loss of response to previous treatment of UC with tofacitinib, upadacitinib, or other systemic janus kinase (JAK) inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Remission at Week 12 | At Week 12 | Clinical remission was defined as modified Mayo Score (mMS) of ≤ 2, including stool frequency subscore ≤ 1, rectal bleeding subscore=0, \& endoscopy subscore ≤ 1 (score of 1 modified to exclude friability). MMS is a composite of 3 Mayo Score assessments, each scored on a scale from 0-3. The total score ranges from 0-9, with higher scores indicating more severe disease: stool frequency (0=Normal number of stools, 1=1-2 more stools than normal, 2=3-4 more stools than normal, 3=5 or more stools than normal); rectal bleeding (0=No blood seen or no bowel movement, 1=Stool with streaks of blood, 2=Stool with more than streaks of blood, 3=Blood alone passed); centrally read endoscopy (0=Normal appearance of mucosa, 1=Mild disease \[erythema, decreased vascular pattern\], 2=Moderate disease \[marked erythema, absent vascular pattern, friability, erosions\], 3=Severe disease \[spontaneous bleeding, ulceration\]). Percentages have been rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response at Week 12 | At Week 12 | Clinical response was defined as decrease from baseline in mMS of ≥ 2 \& ≥ 30% reduction from baseline and also decrease in rectal bleeding subscore of ≥ 1 or absolute rectal bleeding subscore of ≤ 1. MMS is a composite of 3 Mayo Score assessments, each scored on a scale from 0-3. The total score ranges from 0-9, with higher scores indicating more severe disease. Rectal bleeding scores are: 0=No blood seen or no bowel movement, 1=Stool with streaks of blood, 2=Stool with more than streaks of blood, 3=Blood alone passed. Percentages have been rounded off. |
| Percentage of Participants With Endoscopic Improvement at Week 12 | At Week 12 | Endoscopic improvement was defined as a Mayo endoscopy subscore of ≤ 1 (score of 1 modified to exclude friability). Endoscopy scores were based on interpretation by a blinded central reader. The Mayo Score consists of participant-reported outcomes (stool frequency, rectal bleeding), endoscopy, and clinician-reported outcome (Physician's Global Assessment) components. The Mayo endoscopy sub-score ranges from 0 to 3 (0= No inflammation; 1= Mild inflammation \[erythema, decreased vascular pattern\]; 2=Moderate inflammation \[marked erythema, absent vascular pattern, and friability\]; 3= Severe inflammation \[ulceration and spontaneous bleeding\]), with higher scores indicating more severe disease. Percentages have been rounded off. |
| Percentage of Participants With Endoscopic Remission at Week 12 | At Week 12 | Endoscopic remission was defined as a Mayo endoscopy subscore of 0. Endoscopy scores were based on interpretation by a blinded central reader. The Mayo Score consists of participant-reported outcomes (stool frequency, rectal bleeding), endoscopy, and clinician-reported outcome (Physician's Global Assessment) components. The Mayo endoscopy sub-score ranges from 0 to 3 (0= No inflammation; 1= Mild inflammation \[erythema, decreased vascular pattern and mild friability\]; 2=Moderate inflammation \[marked erythema, absent vascular pattern, and friability\]; 3= Severe inflammation \[ulceration and spontaneous bleeding\]), with higher scores indicating more severe disease. Percentages have been rounded off. |
| Number of Participants With Adverse Events (AEs) | Induction period: From treatment initiation up to 10 weeks follow-up after the final dose (up to 22 weeks); ATE period: From treatment initiation up to 10 weeks follow-up after the final dose (up to 56 weeks) | An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; Any new disease or exacerbation of existing disease; Recurrence of an intermittent medical condition not present at baseline; Any deterioration in a laboratory value or other clinical test, associated with symptoms or leads to change in study treatment or concomitant treatment or discontinuation from study treatment; AEs related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment. |
| Serum Concentration of Vixarelimab at Specified Timepoints | Weeks 0, 1, 2, 4, 8, 12, and study completion/early termination (up to 22 weeks) | — |
| Induction: Number of Participants With Anti-drug Antibodies (ADAs) | Baseline and post-baseline visits (up to 12 weeks) | Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). The total number of participants who developed ADAs to vixarelimab was determined by summing the ADA-positive participants across all timepoints. |
Countries
Brazil, China, Czechia, France, Greece, Italy, Mexico, Poland, Serbia, South Korea, Taiwan, United States
Contacts
STUDY_DIRECTORClinical Trial
Genentech, Inc.
Participant flow
Recruitment details
A total of 79 participants with active moderate to severe ulcerative colitis (UC) took part in the study at 43 centers across 12 countries from 1 May 2024 to 16 June 2025.
Pre-assignment details
Participants were randomized in a 1:1:1 ratio to 3 cohorts & received Vixarelimab, every 2 weeks (Q2W); Vixarelimab, every 4 weeks (Q4W), or Placebo, Q2W. The study was divided into two periods: Induction period and an optional Active Treatment Extension (ATE) period. Participants who completed the induction period could optionally continue treatment in the ATE period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 43.4 years STANDARD_DEVIATION 16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 63 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 13 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 15 | 0 / 10 | 0 / 17 |
| other Total, other adverse events | 8 / 27 | 9 / 26 | 3 / 26 | 9 / 15 | 5 / 10 | 8 / 17 |
| serious Total, serious adverse events | 0 / 27 | 3 / 26 | 1 / 26 | 1 / 15 | 0 / 10 | 0 / 17 |
Outcome results
None listed