A Study to Assess Adverse Events and Change in Disease Activity From Intravenous (IV) and Subcutaneous (SC) Lutikizumab in Adult Participants With Active Ulcerative Colitis (Horizon)

AbbVie

Status and phase: Enrolling; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: Lutikizumab Matching Placebo; Drug: Adalimumab Matching Placebo; Drug: Adalimumab; Drug: Lutikizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06257875

M23-703

2023-505678-14-00 (Other Identifier)

Details and patient eligibility

About

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 open label lutikizumab. Around 200 adult participants with UC will be enrolled at approximately 280 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 open-label 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, blinded 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

200 participants in 8 patient groups

Induction Group 1

Experimental group

Description:

Participants will receive Dose 1 of IV lutikizumab at Baseline followed by SC lutikizumab throughout induction. Adalimumab placebo will be utilized to maintain the blind.

Treatment:

Drug: Lutikizumab

Drug: Adalimumab Matching Placebo

Drug: Lutikizumab

Induction Group 2

Experimental group

Description:

Participants will receive Dose 2 of IV lutikizumab at Baseline followed by SC lutikizumab throughout induction. Lutikizumab placebo and adalimumab placebo will be utilized to maintain the blind.

Treatment:

Drug: Lutikizumab

Drug: Adalimumab Matching Placebo

Drug: Lutikizumab

Induction Group 3

Experimental group

Description:

Participants will receive adalimumab per label throughout induction. Lutikizumab placebo will be utilized to maintain the blind.

Treatment:

Drug: Adalimumab

Drug: Lutikizumab Matching Placebo

Drug: Lutikizumab Matching Placebo

Maintenance Group 1

Experimental group

Description:

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. Adalimumab placebo will be utilized to maintain the blind.

Treatment:

Drug: Lutikizumab

Drug: Adalimumab Matching Placebo

Drug: Lutikizumab

Maintenance Group 2

Experimental group

Description:

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. Lutikizumab placebo and adalimumab placebo will be utilized to maintain the blind.

Treatment:

Drug: Lutikizumab

Drug: Adalimumab Matching Placebo

Drug: Lutikizumab Matching Placebo

Drug: Lutikizumab

Drug: Lutikizumab Matching Placebo

Maintenance Adalimumab

Experimental group

Description:

Participants who respond to adalimumab induction group 3 will continue to receive adalimumab per label in the maintenance period. Lutikizumab placebo will be utilized to maintain the blind.

Treatment:

Drug: Adalimumab

Drug: Lutikizumab Matching Placebo

Drug: Lutikizumab Matching Placebo

Maintenance Non-Responders

Experimental group

Description:

Participants who do not respond to study drug at the end of induction period will receive open label SC lutikizumab in the maintenance period.

Treatment:

Drug: Lutikizumab

Drug: Lutikizumab

Optional Long-Term Extension (LTE)

Experimental group

Description:

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 blinded LTE.

Treatment:

Drug: Lutikizumab

Drug: Adalimumab

Drug: Lutikizumab