Primary Objective: to evaluate arterial or synovial 89Zr-Df-crefmirlimab uptake on PET/CT in patients with GCA or RASecondary objectives are:1. Assessment of the relationship between 89Zr-Df-crefmirlimab uptake and the presence of CD8 T cells in…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Synovial and bursal disorders
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoints: The main endpoints are arterial 89Zr-Df-crefmirlimab
uptake in patients with newly-diagnosed GCA, and synovial 89Zr-Df-crefmirlimab
uptake in patients with active RA.
Secondary outcome
Secondary endpoints include:
1) the relationship between 89Zr-Df-crefmirlimab uptake in temporal arteries
and the presence of CD8 T cells in histological analysis of temporal artery
biopsy in patients with newly-diagnosed, cranial GCA
2) the relationship between 89Zr-Df-crefmirlimab uptake and clinical joint
assessment and histological analysis of synovial tissue in patients with RA.
Background summary
Giant cell arteritis (GCA) and rheumatoid arthritis (RA) are both auto-immune
diseases that are characterized by chronic inflammation of large/medium-sized
arteries and joints, respectively. The inflammation in GCA and RA is usually
chronic, and may cause progressive damage of the affected tissues if left
untreated. However, inappropriate treatment may also pose unnecessary risks for
patients due to toxicity of the immunosuppressive treatment. The improvement of
early diagnostics and therapy monitoring remains challenging for both diseases.
A new and reliable tool for diagnostics and therapy monitoring of GCA and RA
could greatly reduce permanent physical damage due to inflammation, as well as
inappropriate use of immunosuppressive treatments.
A new and promising approach to visualize arterial and synovial inflammation
might be to combine positron emission tomography (PET) with novel tracers that
target specific immune cells in affected tissues. CD8 T cells could be an
important target for this novel imaging approach, since these cells are
abundantly present in the inflamed arterial wall and synovial tissue of
patients with GCA and RA, respectively. Currently, tools are becoming available
from oncology studies to visualize CD8 T cells. ImaginAb has developed
89Zr-Df-IAB22M2C, an 80 kDa minibody (Mb) with a high affinity for the CD8
glycoprotein. The minibody is conjugated with deferoxamine (Df) and
radiolabeled with the positron emitting radionuclide Zirconium-89 (89Zr).
89Zr-Df-crefmirlimab was designed to enable whole body PET imaging of CD8+
(positive) cells. We hypothesize that 89Zr-Df-crefmirlimab PET may aid the
detection of inflammation in GCA and RA, given the important role of CD8+ T
cells in the pathobiology of both diseases. This could potentially lead to
better treatment decisions in patients with GCA and RA.
Study objective
Primary Objective: to evaluate arterial or synovial 89Zr-Df-crefmirlimab uptake
on PET/CT in patients with GCA or RA
Secondary objectives are:
1. Assessment of the relationship between 89Zr-Df-crefmirlimab uptake and the
presence of CD8 T cells in histological analysis of the temporal artery biopsy
in patients with newly-diagnosed, cranial GCA
2. Assessment of the relationship between 89Zr-Df-crefmirlimab uptake and
clinical joint assessment and histological analysis of synovial tissue in
patients with RA.
Study design
Study design: A proof of concept, multicentre, prospective study.
Intervention: A single 89Zr-Df-crefmirlimab PET/CT scan will be performed in
patients with GCA and RA. Synovial biopsy will be obtained from all patients
with RA for research purposes only. If a temporal artery biopsy has been
performed as part of standard care, patients will be asked for permission to
use remaining tissue to evaluate the biopsies for the presence of CD8 T cells.
Intervention
89Zr-Df-crefmirlimab PET/CT
Study burden and risks
89Zr-Df-crefmirlimab is a radioactive compound and therefore, will cause
radiation burden to the patient. The projected effective dose after receiving
18.5 ± 20% MBq (0.5 mCi) of 89Zr-Df-crefmirlimab is 12 mSv. For patients
scanned with PET/CT scanners a low dose attenuation correction CT scan, which
has an effective dose of 1 mSv, will be carried out. Patients will undergo a
scan at injection, and at 5 hours, 1 day and 4 days after injection of
89Zr-Df-IAB22M2C, which is associated with an effective dose of 1+1+1+1 = 4
mSv. This will bring the total projected effective dose during the study to
12+4 = 16 mSv. There is a very small chance of bleeding and hematoma due to
synovial biopsy in patients with RA. No direct benefits are expected for study
participants. We expect no risks related to 15 mL blood withdrawal by
venapunction. We aim to provide the proof of concept that the
89Zr-Df-crefmirlimab PET/CT scan might help to more accurately detect arterial
and synovial inflammation in patients with GCA and RA, respectively. An
adequate diagnosis and proper disease monitoring of GCA and RA are essential to
prevent the development of disease complications, while minimizing unnecessary
exposure to immunosuppressive treatment. We see this proof of concept study
with CD8 T cell imaging by positron emission tomography with 89Zr-Df-IAB22M2C,
as the way to organize a breakthrough in the field of GCA and RA diagnostics.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
Giant cell arteritis
- Age > 50 years
- Erythrocyte sedimentation rate (ESR) >=50 mm/hr or C-reactive protein (CRP) >=
10 mg/L
- Clinical symptoms of GCA present at time of inclusion:
• Large vessel GCA (at least one of the following): constitutional symptoms
(fatigue, fever, weight loss, and/or night sweats), limb claudication, or
symptoms of polymyalgia rheumatica (i.e. shoulder and/or hip girdle pain
associated with morning stiffness)
• Cranial GCA (at least one of the following): new-onset localized headache,
scalp tenderness, temporal artery abnormality (thickening, tenderness, and/or
decreased pulsation), ischemia-related vision loss, stroke, transient ischemic
attack, jaw or tongue claudication (pain upon mastication).
- Imaging findings or temporal artery biopsy findings consistent with GCA at
the time of inclusion
• Large vessel GCA as suggested by ultrasonography or FDG-PET/CT
• Cranial GCA as suggested by ultrasonography FDG-PET/CT or temporal artery
biopsy and confirmed by temporal artery biopsy
- Patients must be able to adhere to the study appointments and other protocol
requirements.
- Patients must be capable of giving informed consent and the consent must have
been obtained prior to the study related procedures.
Rheumatoid arthritis
- Patients must be at least 30 years of age
- Diagnosis of rheumatoid arthritis according to the 2010 ACR/EULAR Rheumatoid
Arthritis classification criteria.
- Patients with clinically active disease as assessed by a physician; with
arthritis in at least one wrist, knee or ankle joint and have a clinical
indication to initiate or escalate 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
- Non-steroidal anti-inflammatory drugs (NSAID) is permitted, provided that
there is a stable dose for at least 4 weeks prior to inclusion
- Patients must be able to adhere to the study appointments and other protocol
requirements
- Patients must be capable of giving informed consent and the consent must have
been obtained prior to the study related procedures.
Exclusion criteria
Giant cell arteritis
- Age <= 50 years
- Use of oral, intravenous or intramuscular glucocorticoids within 4 weeks
prior to inclusion.
- Use of disease-modifying antirheumatic drugs (DMARD) within 3 months prior to
inclusion.
- Treatment with any investigational drug within 3 months prior to inclusion.
- Known pregnancy or breast feeding
- Research-related radiation exposure (cumulative >=5 mSv) in the year before
inclusion.
- Urinary or faecal incontinence
Rheumatoid arthritis
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Age < 30 years
- Use of intra-articular, intramuscular or intravenous corticosteroids within 4
weeks prior to inclusie
- Treatment with any investigational drug within the previous 3 months
- Known pregnancy or breast feeding
- Research related radiation exposure (cumulative >=5 mSv) in the year before
inclusion
- Urinary or faecal incontinence
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 |
|---|---|
| Other | 2022-002822-28 |
| EudraCT | EUCTR2022-002822-28-NL |
| CCMO | NL82421.042.22 |