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

NCT01275508 | Completed Phase 1

• 2 other identifiers: FITC-ADA 01-20102010-018959-99
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Crohn's Disease

Keywords

Subjects with active Crohn's disease; Safety and tolerability of FITC-Adalimumab; Intestinal topical application

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Visual identification of FITC-Adalimumab positive intestinal mucosal cells

  One minute after administration of FITC-Adalimumab

• Number of FITC-Adalimumab positive intestinal mucosal cells

  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.

  Three months after administration of FITC-Adalimumab

Study Arms (1)

FITC-Adalimumab

EXPERIMENTAL

Drug: FITC-Adalimumab

Interventions

FITC-Adalimumab DRUG

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.

FITC-Adalimumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead
• Abbott: collaborator

Study Sites (1)

Medizinische Klinik I, University Hospital Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Related Publications (4)

• Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, Schreiber S, Byczkowski D, Li J, Kent JD, Pollack PF. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007 Jan;132(1):52-65. doi: 10.1053/j.gastro.2006.11.041. Epub 2006 Nov 29.

  PMID: 17241859 BACKGROUND

• Keller R, Winde G, Terpe HJ, Foerster EC, Domschke W. Fluorescence endoscopy using a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen in patients with colorectal carcinoma and adenoma. Endoscopy. 2002 Oct;34(10):801-7. doi: 10.1055/s-2002-34254.

  PMID: 12244502 BACKGROUND

• Kiesslich R, Burg J, Vieth M, Gnaendiger J, Enders M, Delaney P, Polglase A, McLaren W, Janell D, Thomas S, Nafe B, Galle PR, Neurath MF. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology. 2004 Sep;127(3):706-13. doi: 10.1053/j.gastro.2004.06.050.

  PMID: 15362025 BACKGROUND

• Kiesslich R, Goetz M, Vieth M, Galle PR, Neurath MF. Technology insight: confocal laser endoscopy for in vivo diagnosis of colorectal cancer. Nat Clin Pract Oncol. 2007 Aug;4(8):480-90. doi: 10.1038/ncponc0881.

  PMID: 17657253 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Markus Neurath, MD PhD

  Medizinische Klinik I, University Hospital Erlangen

  STUDY DIRECTOR

• Raja Atreya, MD, PhD

  Medizinische Klinik I, University Hospital Erlangen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2011
• First Posted: January 12, 2011
• Study Start: January 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: September 14, 2012

Record last verified: 2012-09

Locations

DE (1)