Evaluation of Risankizumab, ABBV-382, and Lutikizumab in Adult Patients with Moderate to Severe Crohn's Disease: A Phase 2a Multicenter Randomized Study

The primary objective of this Phase 2a multicenter, randomized platform study is to evaluate the **safety** and **efficacy** of targeted therapies (TaTs) in adult subjects with moderate to severe **Crohn's Disease**. Additionally, the study aims to assess the mechanistic profile of these therapies. This is clinically relevant as it seeks to provide insights into the potential benefits and risks associated with these targeted treatments, which could lead to improved management strategies for patients suffering from this chronic inflammatory bowel disease.

The clinical trial involves a total of **500 participants** diagnosed with **Moderate to Severe Crohn’s Disease**. The study population includes both male and female adults aged between 18 and 75 years, with a body weight of at least 40 kg at baseline. Participants must have a confirmed diagnosis of Crohn's Disease for a minimum of three months prior to the baseline, supported by biopsy results. The trial population was selected based on specific inclusion criteria, including a Crohn's Disease Activity Index (CDAI) of 220 or higher at baseline and endoscopic evidence of mucosal inflammation. Participants must also have demonstrated intolerance or inadequate response to certain categories of drugs, such as oral locally acting steroids, systemic steroids, immunomodulators, or targeted therapies. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection process.

The clinical trial is designed to evaluate the safety and efficacy of targeted therapies for the treatment of adult subjects with **moderate to severe Crohn's disease**. This is a Phase 2a, multicenter, randomized, double-blind, controlled study. The trial will involve the administration of investigational products, including **risankizumab** and other biologically derived agents, through various routes such as subcutaneous injection and intravenous infusion. The study is expected to commence recruitment on November 30, 2024, and conclude by July 25, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body weight, and a confirmed diagnosis of Crohn's disease. The screening will also assess the Crohn's Disease Activity Index (CDAI) and endoscopic evidence of mucosal inflammation. Following the screening, eligible participants will be randomized to receive the investigational product or a control. The primary endpoint is the achievement of endoscopic remission at Week 12, with secondary endpoints including clinical remission per CDAI and stool frequency/abdominal pain score at the same time point.

The trial will include follow-up visits to monitor safety and efficacy, with assessments conducted at regular intervals. The end-of-study visit will occur after the final treatment period, which varies depending on the investigational product, with a maximum treatment period of up to 84 weeks for some products. Participant involvement is expected to last for the duration of the treatment period plus any additional follow-up required for safety assessments. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or failure to adhere to the study protocol.

The clinical trial involves the administration of several experimental medications, each with distinct pharmaceutical forms, dosages, and routes of administration. **ABBV-066**, containing the active substance **risankizumab**, is provided as a **solution for injection in a pre-filled syringe**. This medication is administered via **subcutaneous injection**. The maximum treatment period for ABBV-066 is 84 weeks. The medication is of biological/biotechnological origin, and participant compliance is monitored throughout the study.

Another formulation of **ABBV-066**, also containing **risankizumab**, is available as a **solution for infusion**. This formulation is administered through **intravenous infusion**. The maximum treatment period for this formulation is 12 weeks. As with the previous formulation, it is of biological/biotechnological origin, and compliance is closely monitored.

**ABBV-382** is another investigational product used in the trial. It is a **humanized IgG1 kappa monoclonal antibody against alfa4beta7 integrin** and is available as a **solution for injection/infusion**. This medication can be administered via **intravenous, subcutaneous, or intramuscular routes**. The maximum treatment period for ABBV-382 is 24 weeks. It is a humanized, recombinant IgG1 monoclonal antibody with FcγR binding ability, and participant adherence to the dosing schedule is monitored.

Lastly, **Lutikizumab**, also known as **ABT-981**, is included in the study. It is provided as a **solution for injection** and is administered via **subcutaneous injection**. The maximum treatment period for Lutikizumab is 24 weeks. This medication is of biotechnological origin, and compliance with the administration schedule is ensured through regular monitoring.

Throughout the trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The study focuses on evaluating the safety, efficacy, and mechanistic profile of these targeted therapies in adult subjects with moderate to severe Crohn's disease. Compliance with the dosing schedules is a critical component of the trial, ensuring the integrity and reliability of the study outcomes.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the achievement of endoscopic remission at Week 12. Secondary endpoints include clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12, clinical remission per stool frequency (SF)/abdominal pain score (APS) at Week 12, and endoscopic response at Week 12. These endpoints will be measured and collected at specified timepoints, with the primary focus on Week 12 assessments. The trial aims to evaluate the efficacy of targeted therapies in adult subjects with moderate to severe **Crohn's Disease**. The assessments will be conducted using validated scales and methods appropriate for the endpoints, ensuring accurate and reliable data collection and analysis.