General- To determine the safety of OTL38 in IBD and rheumatoid arthritis patients by monitoring of vital signs during tracer infusion and evaluating possible (severe) adverse events (SAE/AEs).RA- To determine the feasibility of molecular…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
General
- Evaluating vital parameters, adverse events (AE), serious adverse events
(SAE) and suspected unexpected serious adverse reactions (SUSAR) for safety
assessment.
RA
- Macroscopic fluorescence signals (target-to-background ratio) for detection
of inflammation tissue, high disease activity, during imaging using a
wide-field fluorescence camera.
IBD
- Macroscopic fluorescence signals (target-to-background ratio) for detection
of inflammation tissue, high disease activity, during endoscopy using
fluorescence endoscopy
Secondary outcome
RA
- Correlation between fluorescence imaging to the clinical disease activity
score (DAS28-score).
- Quantification of in vivo fluorescence signals and optical properties through
analysis of MDSFR/SFF spectroscopy measurements.
IBD
- Quantification of fluorescence in vivo and ex vivo through analyses of
MDSFR/SFF spectroscopy measurements;
- Standard histopathological examination to correlate fluorescence and
non-fluorescence signals detected in vivo with histology using in vivo obtained
biopsies;
- The localization and distribution of the OTL38 fluorescent signal at cell
level observed in vivo by CLE.
- Correlation between fluorescence imaging to the clinical disease activity
score, the Mayo and SCCAI score, for ulcerative colitis.
- Correlation between fluorescence imaging to the clinical disease activity
score, the CDAI and SES-CD score, for Crohn*s disease.
- Fluorescence microscopy to correlate fluorescence to localization of
inflammatory cells and especially macrophage infiltration.
Other study parameters
- Patient characteristics (age, BMI, sex, medical history, blood pressure,
pulse and temperature before and after tracer administration)
Background 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. In this feasibility study, we aim to
evaluate the safety and feasibility of the NIR tracer OTL38 for monitoring
disease activity in inflammatory diseases rheumatoid arthritis and inflammatory
bowel disease. We hypothesize 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. We
believe that this approach can improve treatment and diagnosis of patients with
inflammatory disease.
Study objective
General
- To determine the safety of OTL38 in IBD and rheumatoid arthritis patients by
monitoring of vital signs during tracer infusion and evaluating possible
(severe) adverse events (SAE/AEs).
RA
- To determine the feasibility of molecular fluorescence imaging using the
tracer OTL38 targeting the folate β receptor on activated macrophages for the
evaluation of disease activity in patients with rheumatoid arthritis.
IBD
- To determine the feasibility of fluorescence molecular endoscopy (FME) and
MDSFR/SFF spectroscopy using the tracer OTL38 targeting the folate β receptor
on activated macrophages for the evaluation of disease activity in patients
with ulcerative colitis.
- To determine the feasibility of fluorescence molecular endoscopy (FME) and
MDSFR/SFF spectroscopy using the tracer OTL38 targeting the folate β receptor
on activated macrophages for the evaluation of disease activity in patients
with Crohn*s disease.
Study design
RA
Rheumatoid arthritis patients will be imaged using a near infrared (NIR) wide
field camera (figure 1). Both hands (affected and/or unaffected) will be imaged
with the SurgVision intraoperative camera in combination with the Vault system,
a black box, to provide a standardized measurement environment. Both the
palmar and dorsal side of the hands will be imaged. Furthermore, MDSFR/SFF
spectroscopy measurements will be performed on three joints per hand as
visualized in the DAS28-score.
Optionally: patients will be asked to have the fluorescence imaging and
MDSFR/SFF measurements each hour after the end of tracer infusion with a
maximum of 6 hours (in consultation with the patient) after the tracer infusion
has stopped. If not, fluorescence imaging will only take place once after 2-3
hours.
IBD
IBD patients will be imaged during a standard colonoscopy procedure using NIR
endoscopy. First, high definition white-light (HD-WL) endoscopy will be
performed. During HD-WL all suspicious, inflamed tissue will be identified
according to standard clinical care. For both UC and CD, both a clinical and
endoscopic disease activity score will be calculated. For the ulcerative
colitis group, the Mayo score and Simple Clinical Colitis Activity Index
(SCCAI) will be used and for the Crohn*s disease group the Crohn's Disease
Activity Index (CDAI) and Simple Endoscopic Score for Crohn Disease (SES-CD).
Second, molecular fluorescence endoscopy (FME) will be performed. All inflamed
areas identified with HD-WL will be visualized again for fluorescence signals,
as well as possible additional fluorescence areas. MDSFR/SFF spectroscopy will
be performed in vivo, to quantify the inflamed and normal colon mucosa. These
spectroscopy measurements are essential since despite the use of NIR excitation
and fluorophores, tissue specific differences in the optical properties of the
colon have shown to have strong influence on the amount of fluorescence signal
that is measured under wide field illumination endoscopy. Last, confocal
endomicroscopy will be performed on both inflamed and normal mucosa. In
addition, biopsies will be taken from normal mucosa and inflamed mucosa.
Intervention
RA
Score - the disease activity will be scored according to the symptom-based
scoring method used in rheumatology (DAS28-score).
Wide-field fluorescence imaging - Fluorescence imaging will be performed using
the SurgVision F2 multispectral fluorescence imaging system combined with the
SurgVision Vault system. The hands of the patient will be placed one by one
inside the black box and multiple fluorescence images and videos will be taken.
Both the palmar and distal side will be imaged of both hands.
MDSFR/SFF spectroscopy - MDSFR/SFF spectroscopy will be performed using the
system from the Erasmus MC including a fiber. Measurements will be taken from
one unaffected joint if possible (both palmar and dorsal side of the joint. And
of a maximum of three affected joints per hand and if present one unaffected
joint (both palmar and dorsal side of the joint).
IBD
The disease score will be assessed according to the HD-WL images. The Mayo and
SCCAI score will be used for ulcerative colitis patients and the CDAI and
SES-CD score for Crohn*s disease patients.
First, HD-WL endoscopy will be performed to identify and localize the inflamed
area. Then FME will be performed to assess fluorescent signals in inflammation
tissue and normal tissue. MDSFR/SFF spectroscopy will be used to quantify the
fluorescent signals. Last, confocal endomicroscopy will be performed on both
the inflamed and normal mucosa. After endoscopic observation, biopsies will be
taken to a maximum of 28 biopsies. A maximum of 4 biopsies will be taken from
normal tissue, a maximum of 16 biopsies in an inflammation area. If a
difference between low and high activity areas can be defined based on the
white light images, biopsies will be taken from both areas. A maximum of 8
biopsies can be taken from additional areas. Biopsies will be only taken if
judged safe by the gastroenterologist.
Study burden and risks
For the participating patients, there is no diagnostic or treatment benefit
related to the study. Participation may possibly produce useful scientific data
for the future. Risks related to the administration of OTL0038 are described in
the IMPD (version May 16th 2019) and section 6.4 of this document. The
investigational procedures are extensively described in section 3. The risks of
fluorescence endoscopy are comparable to a clinical ileocolonoscopic, very
minimal. The biopsies take at both fluorescence endoscopic procedures have a
small risk of causing superficial bleeding. Most bleedings coagulate
spontaneously. If not, which is very uncommon, the gastroenterologist will
coagulate the small bleeding.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
Rheumatoid arthritis cohort
• 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.
IBD cohort
- 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
Rheumatoid arthritis cohort
• 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.
IBD cohort
• 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-004770-10-NL |
| ClinicalTrials.gov | NCT03938701 |
| CCMO | NL68577.042.18 |