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: Adalimumab

Drug: Lutikizumab Matching Placebo

Drug: Adalimumab Matching Placebo

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 subjects with 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 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.

In the Induction Period, participants will be randomized to receive intravenous (IV) and subcutaneous (SC) lutikizumab or SC adalimumab for 12 weeks. 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 until Week 52. Participants who do not respond to treatment will receive open-label SC lutikizumab until Week 52.

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 exposure to adalimumab (including biosimilars). Note: Subject may be enrolled if 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 7 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: Lutikizumab Matching Placebo

Drug: Adalimumab

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

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: Lutikizumab Matching Placebo

Drug: Adalimumab

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