Efficacy of Vedolizumab Versus Adalimumab Dose Intensification in Crohn's Disease Patients with Secondary Loss of Response to Adalimumab

The primary objective of this study is to evaluate the **efficacy** of a Vedolizumab treatment strategy compared to an Adalimumab (ADA) dose optimization strategy in patients with **Crohn's disease** who have experienced a loss of secondary response and/or exhibit high biomarker activity on standard-dose Adalimumab maintenance therapy. The assessment focuses on achieving clinical and biomarker remission at 24 weeks. This is clinically relevant as it aims to determine the most effective treatment strategy for maintaining remission in patients who do not respond adequately to standard Adalimumab therapy.

Secondary objectives include evaluating the impact of Vedolizumab versus Adalimumab dose optimization on several outcomes:

• Deep remission at week 24 without treatment failure
• Treatment failure at weeks 24 and 52
• Percentage of adverse events at weeks 24 and 52
• Symptomatic remission at week 24
• Evolution of the IBDQ-32 quality-of-life score at week 24
• Clinical and biomarker remission rates at weeks 12 and 52
• CDST score for prediction of clinical remission and biomarkers at inclusion in each treatment arm
• Mucosal remission healing rates at weeks 24 and 52

The clinical trial involves participants diagnosed with **Crohn's disease**, focusing on individuals who have experienced a primary response to Adalimumab but have subsequently shown a loss of response or high biomarker activity despite adequate therapeutic levels. The study population includes both male and female subjects, with an age range spanning from young adults to middle-aged individuals. Participants are required to be major patients who have provided consent and are affiliated with or entitled to a social security scheme. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria emphasize the need for participants to have a history of response to Adalimumab, ensuring a specific focus on those with secondary response loss or elevated biomarker activity. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **vedolizumab** treatment compared to **adalimumab** dose optimization in patients with **Crohn's disease** who have experienced a loss of response or high biomarker activity on standard-dose adalimumab maintenance therapy. This study is a randomized, multicenter, controlled trial with a primary objective to assess clinical and biomarker remission at 24 weeks. The trial is expected to commence recruitment on December 1, 2023, and conclude by January 1, 2027, with a maximum treatment period of 52 weeks for participants.

Participants will be randomly assigned to either the vedolizumab treatment group or the adalimumab dose optimization group. The trial will follow a double-blind design to ensure unbiased results. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria such as a primary response to adalimumab and adequate therapeutic levels, followed by regular follow-up visits at specified intervals to monitor clinical and biomarker responses. The end-of-study visit will occur at the conclusion of the 52-week treatment period or upon early termination.

The expected length of participant involvement is up to 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The primary endpoint is the comparison of clinical and biomarker remission rates at 24 weeks, while secondary endpoints include deep remission, treatment failure rates, adverse events, and symptomatic remission. The study will also analyze the evolution of the IBDQ-32 score and the CDST score for predicting remission. Participants will be monitored closely throughout the trial to ensure safety and efficacy of the treatment strategies being evaluated.

The clinical trial involves the administration of **Entyvio**, a pharmaceutical product containing the active substance **vedolizumab**. Entyvio is formulated as a **powder for concentrate for solution for infusion** and is administered via **intravenous infusion**. The dosage for this trial is set at 300 mg, with a maximum daily dose of 300 mg and a total maximum dose of 3468 mg over a treatment period of up to 52 weeks. Vedolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L04AA33. The product is manufactured by Takeda Pharma A/S and is authorized for use in the European Union under the marketing authorization number EU/1/14/923/001.

The comparator treatment in this trial is **Humira**, which contains the active substance **adalimumab**. Humira is provided as a **solution for injection in a pre-filled syringe** and is administered via **subcutaneous injection**. The dosage regimen for Humira involves a maximum daily dose of 80 mg, with a total maximum dose of 2080 mg over a 52-week treatment period. Adalimumab is also a protein-based therapeutic agent, classified under the ATC code L04AB04. This product is manufactured by AbbVie Deutschland GmbH & Co. KG and holds the marketing authorization number EU/1/03/256/022 in the European Union.

Both treatments are being evaluated in the context of a randomized, multicentre, controlled trial aimed at comparing the efficacy of vedolizumab treatment to adalimumab dose intensification in patients with **Crohn's disease** who have experienced a loss of response or exhibit high biomarker activity on standard-dose adalimumab maintenance therapy. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocols.

The efficacy of the clinical trial will be assessed by comparing the treatment strategies of **Vedolizumab** and **Adalimumab** in patients with Crohn's disease who have experienced a loss of response or exhibit high biomarker activity on standard-dose Adalimumab maintenance therapy. The primary endpoint is the proportion of clinical and biomarker remission at 24 weeks, evaluated through a composite score. Secondary endpoints include deep remission, treatment failure, adverse events, symptomatic remission, and the evolution of IBDQ-32 scores. These will be measured at various timepoints, including weeks 12, 24, and 52.

Clinical remission is defined by a clinical activity score of less than 150, fecal calprotectin levels below 250 mcg/g stools, and CRP levels under 5 mg/L. Additional assessments include ileocolonoscopy with a CDEIS score of less than 3, a Lewis score below 135 in the small bowel using VCE, no disease activity on MRE with a segmental Maria score under 7, and no bowel thickness on ultrasound. Symptomatic remission at week 24 is determined by a stool frequency of less than 3 and an abdominal pain score below 2, alongside the absence of therapeutic failure. The trial will also analyze the CDST score for predicting remission under Vedolizumab and Adalimumab optimization.