Fluorescence Imaging of Risankizumab-800CW in Inflammatory Bowel Disease

Официальное название

Investigating the Safety, Feasibility, and Optimal Dose of Risankizumab-800CW for Visualizing Drug Targeting in Inflammatory Bowel Disease

Обзор

Crohn\'s Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Risankizumab is a human monoclonal antibody against IL23 p19, part of a pro-inflammatory cytokine that mediates the inflammatory response in IBD upon binding to its receptor. Primary non-response to risankizumab is high in both CD and UC. Currently, there are no predictors of response to risankizumab and the actual mechanism of action has not yet been elucidated. To gain better understanding of the drug targeting of risankizumab in IBD, the University Medical Center Groningen (UMCG) developed fluorescently labeled risankizumab (risankizumab-800CW). This study aims to assess the safety and the optimal dose of risankizumab-800CW to visualize and potentially quantify the local drug concentration and predict treatment response in IBD patients using in vivo and ex vivo fluorescence molecular imaging (FMI).

Вмешательства

• Препарат Risankizumab-800CW 4.5 mg
  Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals.
• Препарат Risankizumab-800CW 15 mg
  Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals.
• Препарат Risankizumab-800CW 25 mg
  Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals.
• Препарат Risankizumab-800CW optimal dose
  Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals.

Первичные конечные точки

• Determine the safety of risankizumab-800CW in IBD [Срок оценки: 2-3 days after administration (day of FME procedure)]
• Blood pressure [Срок оценки: Five minutes before, and five and sixty minutes after tracer administration]
• Heart rate [Срок оценки: Five minutes before, and five and sixty minutes after tracer administration]
• Temperature [Срок оценки: Five minutes before, and five and sixty minutes after tracer administration]
• Investigate the feasibility of using ex vivo FMI to detect risankizumab-800CW [Срок оценки: 12 months]
• Investigate the feasibility of using FME to detect risankizumab-800CW signals_1 [Срок оценки: 12 months]
• Investigate the feasibility of using FME to detect risankizumab-800CW signals_2 [Срок оценки: 12 months]
• Investigate the feasibility of using FME to detect risankizumab-800CW signals_3 [Срок оценки: 12 months]
• Determining the optimal imaging dose of risankizumab-800CW [Срок оценки: 12 months]

Вторичные конечные точки (5)

• Investigate a potential correlation of in vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of risankizumab therapy regimen in patients with IBD [Срок оценки: 12 months]
• Investigate a potential correlation of ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of risankizumab therapy regimen in patients with IBD [Срок оценки: 12 months]
• Quantify the fluorescence signals of the tracer in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to tracer dose, in vivo fluorescence intensities and inflammation severity [Срок оценки: 12 months]
• To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies [Срок оценки: 12 months]
• To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about risankizumab mucosal target cells [Срок оценки: 12 months]

Критерии участия

Inclusion Criteria for part A:

• Established IBD diagnosis
• Active disease: clinically active disease of the bowel is defined clinically as at least mild activity using dedicated scoring indices or biochemically active disease as defined by a fecal calprotectin \> 60 μg/g
• Patients must be eligible for risankizumab therapy
• Minimum age of 18 years
• Written informed consent
• Clinical indication for an endoscopic procedure

Inclusion Criteria for part B:

• Established IBD diagnosis
• Patients must be on risankizumab therapy for at least 14 weeks
• Minimum age of 18 years
• Written informed consent
• Clinical indication for an endoscopic procedure

Exclusion Criteria for part A:

• A female study patient who is pregnant or provides breastfeeding
• A female study patient of premenopausal age who does not use any reliable form of contraception at the time of risankizumab-800CW administration and the following 10 weeks
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent
• Prior anti-IL23-specific therapy (IL23/IL12 combination therapy is not an exclusion criteria)
• Active extra gastrointestinal manifestations of Crohn's disease (e.g. uveitis or pyoderma gangrenosum at vital locations)

Exclusion Criteria for part B:

• A female study patient who is pregnant or provides breastfeeding
• A female study patient of premenopausal age who does not use any reliable form of contraception at the time of risankizumab-800CW administration and the following 10 weeks
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent
• Active extra gastrointestinal manifestations of Crohn's disease (e.g. uveitis or pyoderma gangrenosum at vital locations)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Нидерланды · 1 центр

• University Medical Center Groningen — Groningen

Идентификаторы

NCT: NCT06606808 · UMCG 20010 · 2024-515358-25-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗