Safety and Tolerability of FITC-Adalimumab Administration During Confocal Laser Endomicroscopy of the Gut

Study Overview
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Brief Summary
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The scientific objective of the project is to evaluate if the topical administration of Fluoresceinisothiocyanate (FITC)-Adalimumab during the endomicroscopic examination of the gut in Crohn's disease (CD) patients shows an acceptable safety profile. Another objective is to explore whether the use of FITC-Adalimumab as a predictive biomarker might reliably predict patient response to Adalimumab therapy and hence enable optimized utilization of this treatment option.

Official Title
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Prospective, Monocentric, Open-label, Clinical Phase 1 Study to Demonstrate the Safety and Tolerability of FITC-Adalimumab After Single Topical Administration to the Intestinal Mucosa During Endomicroscopy in Patients With Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: FITC-Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trial subjects must meet all of the following inclusion criteria: Male and female subjects from 18 to 70 years of age who are capable of giving informed consent without any restrictions Endoscopically and histologically confirmed diagnosis of Crohn's disease (CD) Manifestation of CD in the colon and/or in the terminal ileum Currently active CD with a CDAI score >150 Clinically inadequate response of CD to systemic glucocorticoids and/or immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate) or glucocorticoid-dependent CD or any contraindication to glucocorticoids Indication for treatment with Adalimumab Indication for intestinal confocal laser endomicroscopy prior to institution of adalimumab therapy Subject is mentally capable of understanding the nature and purpose/conduct of the clinical trial and of following the study staff's instructions Subject has given written informed consent after being informed by an investigator Female subjects additionally must meet at least one of the following criteria: Must be menopausal (at least 12 months' natural amenorrhea or 6 months' amenorrhea with serum FSH >40 mU/mL) or Must have undergone bilateral oophorectomy or hysterectomy or Must be a regular, correct, and reliable user of a contraceptive method with a failure rate of <1% per year (such as oral contraceptives, implants, depot shots, intrauterine device, hormone coil) Must have a vasectomized partner Exclusion Criteria: Subjects must not meet any of the following exclusion criteria: Impaired blood clotting (prothrombin rate <50% and/or PTT >55 sec and/or a platelet count of <50,000/μL) Pregnancy and lactation Contraindications to treatment with adalimumab: Moderate to severe heart failure (NYHA Class III/IV) Active tuberculosis Severe acute infections, e.g. sepsis Opportunistic infections including invasive fungal infections Known hypersensitivity to any of the ingredients of the study product or to any drug with a similar chemical structure Treatment with beta-receptor blocking agents (because of altered symptoms in case of possible anaphylactic reactions to IV fluorescein) Any other condition or medical treatment that, in the investigator's judgment, is not compatible with participation in the trial Individuals who are in a relationship of dependence on or employed by the sponsor or any of the investigators Planned prolonged stay outside the region of the study site, preventing the subject from returning for scheduled visits Participation in any other clinical trial or administration of any investigational drug within the last four weeks prior to the screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FITC-Adalimumab<br> | Drug: FITC-Adalimumab<br>* The study product FITC-Adalimumab will be topically applied via a spray catheter to the intestinal mucosa of Crohn's disease patients during endomicroscopy of the gut. One mL of the diluted study product will be applied each time to overall four selected intestinal areas at a concentration of 20 μg/mL respectively (equivalent to 20 μg of FITC-Adalimumab per area). Total amount applied will be 80 μg FITC-Adalimumab per patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of Fluoresceinisothiocyanate (FITC)-Adalimumab | Local Tolerability: All intestinal mucosal adverse events observed following administration of FITC-Adalimumab. Systemic Safety and Tolerability: Number of SARs during the observation period, i.e., number of SAEs whose occurrence is due to the use of FITC-Adalimumab in this clinical trial. Number of SAEs during the observation period. Number of AEs during the observation period. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual identification of FITC-Adalimumab positive intestinal mucosal cells | Visual identification (yes/no) of FITC-Adalimumab positive intestinal mucosal cells by confocal laser endomicroscopy following labeling with FITC-Adalimumab | One minute after administration of FITC-Adalimumab | 
| Number of FITC-Adalimumab positive intestinal mucosal cells | Number of FITC-Adalimumab positive intestinal mucosal cells as identified by confocal laser endomicroscopy following labeling with FITC-Adalimumab | One minute after administration of FITC-Adalimumab | 
| Correlation between the number of FITC-Adalimumab positive intestinal mucosal cells in inflamed gut sections and therapeutic response to Adalimumab therapy. | Correlation between the number of FITC-Adalimumab positive intestinal mucosal cells in inflamed gut sections and therapeutic response. | Three months after administration of FITC-Adalimumab | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subjects with active Crohn's disease, Safety and tolerability of FITC-Adalimumab, Intestinal topical application