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Trial record 44 of 2721 for:    Rheumatoid Arthritis

Fluorescence Imaging of Disease Activity in IBD and Rheumatoid Arthritis Using OTL38 (AVIATOR)

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ClinicalTrials.gov Identifier: NCT03938701
Recruitment Status : Not yet recruiting
First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Sponsor:
Collaborators:
GlaxoSmithKline
On Target Laboratories, LLC
VU University Medical Center
Information provided by (Responsible Party):
dr. W.B. Nagengast, MD, University Medical Center Groningen

Brief Summary:
Rheumatoid Arthritis (RA) and inflammatory bowel disease (IBD) are both inflammatory diseases caused by a persistent chronic inflammation. A chronic inflammation is caused by the absence of the inflammation response resolution. Currently, diagnosis and disease activity measurements are based on symptom-based scores or on anatomical imaging devices. Both methods are unable to detect both early stages of the disease and early changes in inflammation as a reaction to treatment. Objective, early measures of inflammation could improve diagnosis and in the future therapeutic outcomes by identifying early therapy responders and non-responders. The aim of this feasibility study is to evaluate the safety and feasibility of the near infrared (NIR) tracer OTL38 for monitoring disease activity in inflammatory diseases rheumatoid arthritis and inflammatory bowel disease. The hypothesis is that OTL38 will accumulate in inflamed tissue due to the increased presence of activated macrophages expressing the folate beta receptor, enabling better visualization and monitoring of the inflammation. It is expected that this approach can improve treatment and diagnosis of patients with inflammatory disease.

Condition or disease Intervention/treatment Phase
IBD Rheumatoid Arthritis Drug: OTL38 Device: Fluorescence Imaging Phase 1

Detailed Description:
see brief summary

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Fluorescence Imaging for the Evaluation of Disease Activity in IBD and Rheumatoid Arthritis Using the Fluorescent Tracer OTL38 Targeting the Folate β Receptor: a Single-center Pilot Study
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fluorescence imaging with OTL38

Fluorescence imaging with OTL38 in inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) patients. A non-randomised, non-blinded, prospective, feasibility study.

- Administration of 0.0125 mg/kg OTL38 to a total of 30 patients: 10 with Crohn's disease, 10 with ulcerative colitis and 10 with rheumatoid arthritis.

Drug: OTL38
Intravenous administration of 0.0125 mg/kg OTL38 2-3 hours prior to fluorescence imaging.

Device: Fluorescence Imaging

Fluorescence Imaging Rheumatoid Arthritis (RA):

Open-air camera - a camera that enables detection of fluorescent signals.

Fluorescence Imaging inflammatory bowel disease (IBD):

Molecular Fluorescence Endoscopy - a flexible fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fibre-probe is inserted through the standard working channel of the standard clinical endoscope. Fluorescence imaging will be performed during standard clinical colonoscopy.





Primary Outcome Measures :
  1. Safety: number of participants with symptoms or changes in vital signs (blood pressure, heart rate and temperature) that are related to administration of OTL38 [ Time Frame: Up to 1 hour after stop tracer injection ]

    To determine the safety of OTL38 in inflammatory bowel disease (IBD) and rheumatoid arthritis patients by monitoring of vital signs (blood pressure, heart rate and temperature) before, during and after tracer infusion.

    These vital signs are measured before tracer administration, directly after and then every 15 minutes until 1 hour after tracer administration.


  2. Discrimination of inflamed and normal tissue based on in vivo fluorescence measurements from OTL38 gained during fluorescence imaging of the hand of rheumatoid arthritis patients [ Time Frame: Up to 1 year ]
    The target-to-background will be measured during fluorescence imaging. These results will be related to the gold standard clinical care to evaluate the feasibility of molecular fluorescence imaging using the tracer OTL38 targeting for the evaluation of disease activity in patients with rheumatoid arthritis.

  3. Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from OTL38 gained during fluorescence endoscopy in patients with ulcerative colitis (UC). [ Time Frame: Up to 1 year ]
    The target-to-background will be measured during fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy. These results will be related to the gold standard clinical care to evaluate the feasibility of fluorescence molecular endoscopy using the tracer OTL38 targeting for the evaluation of disease activity in patients with ulcerative colitis.

  4. Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from OTL38 gained during fluorescence endoscopy in patients with Crohn's disease (CD). [ Time Frame: Up to 1 year ]
    The target-to-background will be measured during fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy. These results will be related to the gold standard clinical care to evaluate the feasibility of fluorescence molecular endoscopy using the tracer OTL38 targeting for the evaluation of disease activity in patients with Crohn's disease.

  5. Safety: number of participants with (serious) adverse events that are related to the administration of OTL38 [ Time Frame: Up to 24 hours after tracer injection ]
    (serious) adverse events will be monitored until 24 hours after tracer administration.


Secondary Outcome Measures :
  1. The correlation between the fluorescence intensity and the disease activity measured with the DAS28 in patients with RA. [ Time Frame: Up to 1 year ]

    The DAS28 (Disease Activity Score 28) is developed and validated by the EULAR (European League Against Rheumatism) to measure the progress and improvement of Rheumatoid Arthritis by measuring 28 joints. When looking at these joints, both the number of joints with tenderness upon touching and swelling are counted. Furthermore, the erythrocyte sedimentation rate is measured and a patients assessment of disease activity during the preceding 7 days is measured on a scale between 0 and 100, where 0 is 'no activity' and 100 is 'highest activity possible'.

    DAS28 values range from 0.49 to 9.07 while higher values mean a higher disease activity. A DAS28 below the value of 2.6 is interpreted as Remission. Between 2.6 and 3.2 as low disease activity, and between 3.2 and 5.1 as moderate. Above 5.1 is indicated as high disease activity.


  2. Calculation of optical properties with MDSFR/SFF spectroscopy in patients with RA [ Time Frame: Up to 1 year ]
    To quantify the optical properties, in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy measurements;

  3. The correlation between fluorescence intensity and the disease activity score in ulcerative colitis using the Mayo score; [ Time Frame: Up to 1 year ]

    The full Mayo score evaluates disease activity, based on four parameters: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment. Each parameter can be scored from 0 (inactive disease) to 3 (severe disease activity). The final score is the summation of all four parameters.

    0-2 = remission 3-5 = mild activity 6-10 = moderate activity >10 = severe activity


  4. The correlation between fluorescence intensity and the disease activity score in Crohn's disease using the Harvey-Bradshaw index (HBI). [ Time Frame: Up to 1 year ]

    The HBI ensures systematic collection of clinical data in patients with Crohn's disease considering 5 clinical parameters: patient well-being, abdominal pain, number of liquid or soft stools, abdominal mass and Complications.

    <5 = remission 5-7 = mid activity 8-16 = moderate activity >16 = severe activity.


  5. The correlation and validation of fluorescence signals detected in vivo to the pathology of biopsies for IBD patients; [ Time Frame: Up to 1 year ]
    Pathology findings are correlated to fluorescence signals to determine if pathology results (inflammation) correspond to fluorescence signals (high fluorescence) and vice versa, normal tissue corresponds too low fluorescence signals.

  6. The feasibility of visualising the fluorescence signal of OTL38 in vivo by confocal laser endomicroscopy for IBD patients; [ Time Frame: Up to 1 year ]
    Confocal laser endomicroscopy measurements are taken in vivo during fluorescence endoscopy. These images are compared to pathology results and fluorescence images to see if the device is able to detect the fluorescence signal of OTL38 in tissue.

  7. Quantification of fluorescence signals in vivo and ex vivo of inflamed and normal tissue using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy measurements in IBD patients; [ Time Frame: Up to 1 year ]

    The measurements with MDSFR/SFF are performed on the same tissue: in vivo during endoscopy and ex vivo on the biopsies. Therefore they are considered as one measurement outcome.

    Measurements are taken from both normal tissue and inflammation tissue.


  8. The pharmacokinetics of OTL38 by measuring the plasma concentration of OTL38 at predefined time-points in both IBD and RA patients. [ Time Frame: Up to 1 year ]
    Three blood samples will be taken from the first 3 patients in the RA group and UC group. The first timepoint will be before tracer administration and the second timepoint will be one hour after tracer infusion has stopped. The third timepoint will be either after endoscopic procedure or after imaging procedure of RA (2-3 hours after completion of tracer administration).

  9. The correlation between fluorescence intensity and the disease activity score in ulcerative colitis using the SCCAI; [ Time Frame: Up to 1 year ]
    The SCCAI is a diagnostic questionnaire to assess the severity of symptoms in patients with ulcerative colitis. The score ranges from 0 to 19 based on questions on topics regarding the bowel frequency, urgency of defecation, blood in stool and general health. A score of 5 or higher indicates active disease.

  10. The correlation between fluorescence intensity and the disease activity score in Crohn's disease using the SES-CD score [ Time Frame: Up to 1 year ]
    SES-CD (Simple Endoscopic Score for Crohn Disease) is a endoscopic assessment tool for patients with Crohn's disease. Four parameters are evaluated: ulcers, surface involved by disease, surface involved by ulcerations and narrowings? 0-2 = remission 3-6 = mild endoscopic activity 7-15 = moderate endoscopic activity >15 = severe endoscopic activity



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria Rheumatoid Arthritis:

  • Patient diagnosed with active Rheumatoid Arthritis (RA) in one or both hands by their physician and therefore switching to another biological;
  • Age ≥ 18 years;
  • Prior treatment with one anti-TNF agent is permitted, but may not be a primary failure to any anti-TNF agent (defined as no response within the first 12 weeks of treatment);
  • Treatment with disease modifying anti-rheumatic drugs (DMARDS) and oral corticosteroid up to 10 mg daily is allowed, provided that there is a stable dose for at least 4 weeks prior to inclusion and during the study up to 12 weeks of follow up.
  • Non-steroidal anti-inflammatory drugs (NSAID) is permitted, provided that there is stable dose for at least 4 weeks prior to inclusion and during the study up to 12 weeks of follow up;
  • Written informed consent.

Exclusion Criteria rheumatoid arthritis:

  • • Patients who received methotrexate and folic acid less than 7 days before tracer infusion;

    • Use of intramuscular or intravenous corticosteroids within 4 weeks prior to screening;
    • Concurrent uncontrolled medical conditions;
    • Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
    • Patients with a history of anaphylactic reactions or severe allergies;
    • Patients with a history of allergy to any of the components of OTL38, including folic acid;
    • Treatment with any investigational drug within the previous 3 months.

Inclusion Criteria IBD:

  • Patient diagnosed with active ulcerative colitis or Crohns disease by their physician and therefore switching to another biological;
  • Prior treatment with one anti-TNF agent is permitted, but may not be a primary failure to any anti-TNF agent (defined as no response within the first 12 weeks of treatment)
  • Age ≥ 18 years;
  • Written informed consent.

Exclusion Criteria IBD:

  • Concurrent uncontrolled medical conditions;
  • Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
  • Patients with a history of anaphylactic reactions or severe allergies;
  • Patients with a history of allergy to any of the components of OTL38, including folic acid;
  • Treatment with any investigational drug within the previous 3 months;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03938701


Locations
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Netherlands
University Medical Center Groningen Not yet recruiting
Groningen, Netherlands, 9713 GZ
Contact: W B Nagengast, MD, PhD, PharmD    +31503612620    w.b.nagengast@umcg.nl   
Sponsors and Collaborators
University Medical Center Groningen
GlaxoSmithKline
On Target Laboratories, LLC
VU University Medical Center

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Responsible Party: dr. W.B. Nagengast, MD, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03938701     History of Changes
Other Study ID Numbers: NL68577.042.18
First Posted: May 6, 2019    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:
Fluorescence
OTL38
Folate receptor
Disease activity

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases