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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.

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

Clinicaltrials.gov identifier NCT03938701

Recruitment Status Not yet recruiting

First Posted May 6, 2019

Last update posted April 28, 2021

Study Description

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:IBD
    Rheumatoid Arthritis
  • Intervention/Treatment: Drug: OTL38
    Device: Fluorescence Imaging
  • Phase: Phase 1
Detailed Description

see brief summary

Study Design
  • Study Type: Interventional
  • 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: September 2021
  • Estimated Primary Completion Date: December 2021
  • Estimated Study Completion Date: December 2021
Arms and interventions
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.
Outcome Measures
  • 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. 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.
  • 3. 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.
  • 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 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.
  • 5. 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.
  • 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 clinical 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.
  • 4. The correlation between fluorescence intensity and the endoscopic disease activity score in ulcerative colitis using the Mayo endoscopic subscore; [ Time Frame: Up to 1 year ]
    The endoscopic Mayo Score (Mayo endoscopic subscore) evaluates ulcerative colitis stage, based only on endoscopic exploration. Endoscopic activity is based upon the assessment of a few features, such as the presence of erythema, visibility of the vascular pattern, friability, erosions, spontaneous bleeding and (large) ulcerations. Each score indicates endoscopic activity: 0 = inactive disease tot 3 = severely active disease. 3-5 = mild activity 6-10 = moderate activity >10 = severe activity
  • 5. The correlation between fluorescence intensity and the clinical disease activity score in Crohn's disease using the Crohn's Disease Activity Index (CDAI). [ Time Frame: Up to 1 year ]
    The CDAI quantifies the symptoms of patients with CD. The index consists of 8 factors, each summed after adjustment with a weighting factor. Symptoms are scored over the last 7 days and include: number of soft/liquid stools, general well being, severity of abdominal pain, number of complications, ant-diarrhea drug use, abdominal mass, hematocrit, body weight. Remission is defined as CDAI < 150 and severe disease as CDAI > 450.
  • 6. 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
  • 7. 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.
  • 8. 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.
  • 9. 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.
  • 10. Correlation in IBD between fluorescence intensity and biochemical parameters using faecal calprotectin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) [ Time Frame: Up to 1 year ]
    Values of CRP/ESR and faecal calprotectin at baseline will be assessed to determine the correlation with the target-to-background measured at baseline during fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy.
  • 11. Correlation in IBD between the detected fluorescence signals in vivo and the clinical response to induction therapy at week 14. [ Time Frame: Up to 1 year ]
    Values of clinical disease activity scores (SCCAI for UC and CDAI for CD) will be obtained at week 14 from the patient's electronic medical chart in order to determine the correlation with the target-to-background ratio measured at baseline during fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy.
Eligibility Criteria
  • 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:

- Start first treatment or treatment switch to (another) biological(s) in a patient
diagnosed with active Rheumatoid Arthritis (RA) by their physician in one or both
hands.

- Age ≥ 18 years;

- Written informed consent.

For female subjects who are of childbearing potential, are premenopausal with intact
reproductive organs or are less than 2 years postmenopausal

- A negative pregnancy test must be available

- Willing to ensure that she or her partner uses effective contraception during the
study and for 3 months thereafter.

Exclusion Criteria rheumatoid arthritis:

- Received methotrexate and/or folic acid less than 7 days before tracer infusion;

- Skin type above type 3 according to the Fitspatrick scale;

- Primary failure (no response) within the first 12 weeks after start with any anti-TNF
agent;

- Prescribed disease modifying anti-rheumatic drugs (DMARDs) at a higher dose than 10 mg
and/or no stable dose for at least 4 weeks prior to inclusion;

- Prescribed oral corticosteroids at a higher dose than 10 mg, and/or no stable dose for
at least 4 weeks prior to inclusion;

- Use of intramuscular or intravenous corticosteroids within 4 weeks prior to inclusion;

- Prescribed non-steroidal anti-inflammatory drugs (NSAID) with no stable dose for at
least 4 weeks prior to inclusion

- Concurrent uncontrolled medical conditions according to treating medical physician;

- 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.

- Pregnancy or breast feeding.

Inclusion Criteria IBD:

- Patient diagnosed with clinical active ulcerative colitis or Crohn's disease and
therefore scheduled to switch to (another) biological(s);

- Age ≥ 18 years;

- Written informed consent.

For female subjects who are of childbearing potential, are premenopausal with intact
reproductive organs or are less than 2 years postmenopausal

- A negative pregnancy test must be available

- Willing to ensure that she or her partner uses effective contraception during the
study and for 3 months thereafter.

Exclusion Criteria IBD:

- Concurrent uncontrolled medical conditions;

- 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;

- Pregnancy or breast feeding.

Contacts and Locations
Contacts
Locations

Netherlands
University Medical Center Groningen
Groningen

Sponsors and Collaborators

University Medical Center Groningen

GlaxoSmithKline

On Target Laboratories, LLC

VU University Medical Center

More Information
  • Responsible Party: 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: April 28, 2021
  • Last Verified: April 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by University Medical Center Groningen: Fluorescence
    OTL38
    Folate receptor
    Disease activity
  • Additional relevant MeSH terms: Arthritis Arthritis, Rheumatoid