Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Lutikizumab, Adalimumab
Brief summary
Ulcerative colitis (UC) is a type of inflammatory bowel disease that causes inflammation and bleeding from the lining of the rectum and colon (large intestine). The purpose of this study is to assess how safe and effective lutikizumab is in adult participants with moderate to severe UC and how lutikizumab compares to adalimumab in the treatment of UC. Adverse events and changes in disease activity will be assessed. Lutikizumab is an investigational product being developed for the treatment of moderate to severe UC. Participants are placed in groups called treatment arms. Each group receives a different treatment. In the Induction Period, participants will be randomized into 1 of 3 arms receiving lutikizumab Dose 1, lutikizumab Dose 2, or adalimumab. In the Maintenance Period, participants who responded to lutikizumab will be randomized into 1 of 2 arms of lutikizumab maintenance and participants who responded to adalimumab will continue to receive adalimumab. All participants who did not achieve clinical response per modified Mayo Score at the end of the Induction period will receive lutikizumab. Around 200 adult participants with UC will be enrolled at approximately 200 sites worldwide. During the 12 week Induction Period, participants will be randomized to receive intravenous (IV) and subcutaneous (SC) lutikizumab or SC adalimumab. At the 12 week mark, participants who are on lutikizumab who have responded to treatment will be re-randomized to receive SC lutikizumab at different intervals until Week 52. Participants who are on adalimumab who are responding to treatment will continue to receive adalimumab. Participants who do not respond to treatment will receive SC lutikizumab. Participants who complete the Week 52 visit and in whom therapeutic benefit to study drug is confirmed by the investigator may roll over into an optional, 52-week long-term extension (LTE). There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGLutikizumab
Subcutaneous (SC) Injection
DRUGAdalimumab
SC Injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has had a diagnosis of Ulcerative Colitis (UC) for at least 90 days prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of UC in the assessment of the investigator, must be available. * Active UC with a Modified Mayo Score (mMS) of 5 to 9 points and Mayo Endoscopic Subscore (ESS) of 2 to 3 (confirmed by central review). * Demonstrated inadequate response to, loss of response to, or intolerance to at least one of the following: oral aminosalicylates, corticosteroids, immunomodulators, and/or advanced therapies.
Exclusion criteria
* Current diagnosis of Crohn's Disease (CD) or inflammatory bowel disease-unclassified. * Extent of inflammatory disease limited to the rectum as assessed by screening endoscopy. * Prior inadequate response, intolerance or loss of response to adalimumab (including biosimilars). Note: Participant may be enrolled if he/she discontinued adalimumab for reasons other than those listed above (e.g., loss of insurance) or he/she has been exposed to other advanced therapies, including anti-TNFs other than adalimumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve Endoscopic Improvement | Week 12 | Endoscopic Improvement is defined as Mayo Endoscopic Subscore (ESS) of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal appearance of mucosa; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Number of Participants with Adverse Events (AEs) | Up to approximately Week 104 | An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve Clinical Remission Per Modified Mayo Score (mMS) | Week 12 | Clinical remission on the mMS is defined as Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore \<= 1, AND not greater than baseline. The mMS is a composite score of UC disease activity based on the following 3 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed); ESS, scored from 0 (normal appearance of mucosa) to 3 (severe disease \[spontaneous bleeding, ulceration\]). The overall mMS ranges from 0 to 9 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer. |
| Percentage of Participants who Achieve Clinical Response Per mMS | Week 12 | Clinical response per mMS is defined as decrease from baseline \>=2 points and \>=30%, PLUS a decrease in RBS \>= 1 or an absolute RBS \<=1. The mMS is a composite score of UC disease activity based on the following 3 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed); ESS, scored from 0 (normal appearance of mucosa) to 3 (severe disease \[spontaneous bleeding, ulceration\]). The overall mMS ranges from 0 to 9 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer. |
| Percentage of Participants who Achieve Endoscopic Remission | Week 12 | Endoscopic remission is defined as Mayo Endoscopic Subscore (ESS) of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal appearance of mucosa; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Latvia, Lithuania, New Zealand, Norway, Poland, Puerto Rico, Serbia, Slovenia, South Africa, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Outcome results
None listed