A Multicenter, Randomized Study to Evaluate the Safety and Efficacy of Lutikizumab for Induction and Maintenance Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 156
- Locations
- 191
- Primary Endpoint
- Percentage of Participants who Achieve Endoscopic Improvement
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant has had a diagnosis of 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 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: Subject may be enrolled if he/she discontinued adalimumab for reasons other than those listed above (e.g., loss of insurance) or if he/she has been exposed to other advanced therapies, including anti-TNFs other than adalimumab.
Arms & Interventions
Induction Group 1
Participants will receive Dose 1 of IV lutikizumab at Baseline followed by SC lutikizumab throughout induction.
Intervention: Lutikizumab (Drug)
Induction Group 2
Participants will receive Dose 2 of IV lutikizumab at Baseline followed by SC lutikizumab throughout induction.
Intervention: Lutikizumab (Drug)
Induction Group 3
Participants will receive adalimumab per label throughout induction.
Intervention: Adalimumab (Drug)
Maintenance Group 1
Participants who responded to lutikizumab induction group 1 or 2 will be re-randomized. Participants in this group will receive SC lutikizumab throughout the maintenance period.
Intervention: Lutikizumab (Drug)
Maintenance Group 2
Participants who responded to lutikizumab induction group 1 or 2 will be re-randomized. Participants in this group will receive SC lutikizumab throughout the maintenance period.
Intervention: Lutikizumab (Drug)
Maintenance Adalimumab
Participants who respond to adalimumab induction group 3 will continue to receive adalimumab per label in the maintenance period.
Intervention: Adalimumab (Drug)
Maintenance Non-Responders
Participants who do not respond to study drug at the end of induction period will receive SC lutikizumab in the maintenance period.
Intervention: Lutikizumab (Drug)
Optional Long-Term Extension (LTE)
Participants who complete the maintenance period, are willing/able to inject study drug at home, and in whom therapeutic benefit to study drug is confirmed by the investigator, may participate in the optional 52-week LTE.
Intervention: Lutikizumab (Drug)
Optional Long-Term Extension (LTE)
Participants who complete the maintenance period, are willing/able to inject study drug at home, and in whom therapeutic benefit to study drug is confirmed by the investigator, may participate in the optional 52-week LTE.
Intervention: Adalimumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants who Achieve Endoscopic Improvement
Time Frame: 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)
Time Frame: 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 Outcomes
- Percentage of Participants who Achieve Clinical Remission Per Modified Mayo Score (mMS) at week 12
- Percentage of Participants who Achieve Clinical Response Per mMS at week 12
- Percentage of Participants who Achieve Endoscopic Remission at week 12
Investigators
Global Clinical Trials Helpdesk
Scientific
AbbVie Deutschland GmbH & Co. KG