A Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Intravenous (IV) Infusion and Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. CD may cause tiredness, loose stools with or without bleeding, abdominal pain, weight loss, and fever. This study evaluates how safe and effective ABBV-154 is in participants treated for moderately to severely active CD. Adverse events and change in the disease activity will be assessed. ABBV-154 is an investigational drug being evaluated for the treatment of CD. In the induction period, there is a 1 in 5 chance that participants will be assigned to placebo. Depending on the dose received in the induction period, there is a 1 in 2 or 1 in 3 chance that participants will be assigned to placebo in the maintenance period. Around 265 participants 18-75 years of age with moderately to severely active CD will be enrolled in the study at approximately 200 sites worldwide. The study is compromised of a 12-week double-blind, placebo-controlled induction period, followed by either a 12-week double-blind re-induction period for non-responders or a 40-week double-blind placebo-controlled maintenance period for responders. In the maintenance period, responders will be randomized to receive subcutaneous placebo or ABBV-154 in 2 different doses every other week. Participants in the placebo group who are initial responders will receive ABBV-154 in the maintenance period. There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. 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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of ABBV-154 in Subjects With Moderately to Severely Active Crohn's Disease (CD): AIM-CD

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: ABBV-154
* Drug: Placebo
* Drug: ABBV-154
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Crohn's Disease (CD) for at least 3 months prior to Baseline of the Induction Period. Crohn's Disease Activity Index (CDAI) score 220 to 450 at Baseline of the Induction Period. Endoscopic evidence of mucosal inflammation as documented by an Simple Endoscopic Score for Crohn's Disease (SES-CD) of >= 6 for ileocolonic or colonic disease or SES-CD of >= 4 for isolated ileal disease as scored by a central reader. All eligible scores must exclude the presence of narrowing component. Demonstrated intolerance or inadequate response to one or more of the following biologic agents: infliximab, adalimumab, certolizumab pegol, vedolizumab, natalizumab, ustekinumab, or risankizumab. Exclusion Criteria: - Participants with prior intolerance to adalimumab.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction Phase: ABBV-154 Randomized Dose A<br>Varying doses of ABBV-154 as described in the protocol. | Drug: ABBV-154<br>* Intravenous (IV) Infusion; Subcutaneous Injection<br>|
| Experimental: Induction Phase: ABBV-154 Randomized Dose B<br>Varying doses of ABBV-154 as described in the protocol. | Drug: ABBV-154<br>* Intravenous (IV) Infusion; Subcutaneous Injection<br>|
| Experimental: Induction Phase: ABBV-154 Randomized Dose C<br>Varying doses of ABBV-154 as described in the protocol. | Drug: ABBV-154<br>* Intravenous (IV) Infusion; Subcutaneous Injection<br>|
| Experimental: Induction Phase: ABBV-154 Randomized Dose D<br>Varying doses of ABBV-154 as described in the protocol. | Drug: ABBV-154<br>* Intravenous (IV) Infusion; Subcutaneous Injection<br>Drug: Placebo<br>* Subcutaneous Injection<br>|
| Placebo Comparator: Induction Phase: Randomized Placebo<br>Fixed dose placebo as described in the protocol. | Drug: Placebo<br>* Intravenous (IV) infusion; Subcutaneous Injection<br>|
| Experimental: Re-Induction Phase: ABBV-154 Randomized Dose A<br>Varying doses of ABBV-154 as described in the protocol. | Drug: ABBV-154<br>* Intravenous (IV) Infusion; Subcutaneous Injection<br>|
| Experimental: Re-Induction Phase: ABBV-154 Randomized Dose B<br>Varying doses of ABBV-154 as described in the protocol. | Drug: ABBV-154<br>* Intravenous (IV) Infusion; Subcutaneous Injection<br>|
| Experimental: Maintenance Phase: ABBV-154 Randomized Dose A<br>Fixed dose ABBV-154 every other week. | Drug: ABBV-154<br>* Subcutaneous Injection<br>|
| Experimental: Maintenance Phase: ABBV-154 Randomized Dose B<br>Fixed dose ABBV-154 every other week. | Drug: ABBV-154<br>* Subcutaneous Injection<br>|
| Placebo Comparator: Maintenance Phase: Randomized Placebo<br>Fixed dose placebo every other week. | Drug: Placebo<br>* Subcutaneous Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Endoscopic Response per Simple Endoscopic Score for Crohn's Disease (SES-CD) | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | Week 12 in the Induction Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Remission per Crohn's Disease Activity Index (CDAI) | The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. Clinical remission is defined as CDAI < 150. | Week 12 in the Induction Period | 
| Percentage of Participants Achieving Clinical Remission per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | Clinical remission is defined as average daily liquid or very soft SF <= 2.8 and not worse than Baseline and average daily AP score <= 1 and not worse than Baseline. | Week 12 in the Induction Period | 
| Percentage of Participants Achieving Endoscopic Response per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | Week 40 in the Maintenance Period | 
| Percentage of Participants Achieving Clinical Remission per CDAI | The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. Clinical remission is defined as CDAI < 150. | Week 40 in the Maintenance Period | 
| Percentage of Participants Achieving Clinical Remission per SF/AP | Clinical remission is defined as average daily liquid or very soft SF <= 2.8 and not worse than Baseline and average daily AP score <= 1 and not worse than Baseline. | Week 40 in the Maintenance Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, ABBV-154