We here propose a pilot immuno-PET study in active relapsing MS patients to investigate safety and sensitivity of 89Zr-rituximab in detecting CD20 positive (active) MS lesions and to assess inter-patient variability in 89Zr-rituximab biodistribition…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
89Zr-rituximab uptake in CD20 positive (actieve) MS lesions
Secondary outcome
Inter-patient variability in 89Zr-rituximab biodistribition.
Background summary
Recent concepts of multiple sclerosis (MS) suggest that autoimmune B cells and
humoral immune mechanisms may play key roles in MS. Initial beneficial results
of therapies targeting B cells in patients with autoimmune diseases have been
reported. A recent phase 2 clinical trial showed that rituximab, a chimeric
monoclonal antibody (mAb) against CD20, reduces disease activity in
relapsing-remitting MS; patients treated with rituximab had a substantial
reduction in the number of clinical relapses and contrast-enhancing lesions
(CEL) on magnetic resonance imaging (MRI). However, the rapid effect of
rituximab on acute disease activity suggests that the beneficial mechanism in
MS is not the modulation of soluble autoantibodies. Instead, several other
possible explanations for the effects of rituximab in MS have been suggested.
In fact, the mechanisms underlying the effects of rituximab on disease activity
in MS are unclear.
The introduction of immuno-positron emission tomography (PET), the combination
of PET with mAbs, is an attractive novel option to visualize molecular
interactions. In MS patients, treatment with rituximab labelled with a positron
emitter has the potential for quantification of the interactions of the drug
within the different compartments of the body, especially the CNS, including
active lesions.
Study objective
We here propose a pilot immuno-PET study in active relapsing MS patients to
investigate safety and sensitivity of 89Zr-rituximab in detecting CD20 positive
(active) MS lesions and to assess inter-patient variability in 89Zr-rituximab
biodistribition and targeting of CD20 positive B cells.
Study design
Six active relapsing-remitting MS patients will receive 1000-mg intravenous
infusions of rituximab on study days 1 and 15. Only the first administration
will be partially labelled with the positron emitter Zirconium-89. PET scans
will be performed on day 1, 3 and 6.
Intervention
1000-mg intravenous infusions of rituximab on study days 1 and 15. Only the
first administration will be partially labelled with the positron emitter
Zirconium-89. PET scans will be performed on day 1, 3 and 6.
Study burden and risks
Physical examination
3 x PET scan
2 x MRI
Blood samples
Adverse effects rituximab
Postbus 7057
1007 MB Amsterdam
NL
Postbus 7057
1007 MB Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Diagnosis of MS
EDSS score 0.0 to 5.0
Age between 18 and 50 years
>=1 MS attack(s) in the year prior to screening
>=1 MS attack during treatment with interferon beta or glatiramer acetate
Exclusion criteria
Previous treatment with mitoxantrone, natalizumab or any investigational drug for MS the year before screening
Any progressive form of MS
Inability to undergo MRI with gadolinium administration
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 | EUCTR2009-016580-11-NL |
| CCMO | NL29305.029.09 |