The objective of the study is to assess the safety and tolerability, and to characterize the pharmacokinetics (PK) and pharmacodynamics (e.g., Cerebrospinal fluid [CSF] levels of IL-1β, TSPO positron emission tomography [PET] imaging) of…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and tolerability of selnoflast compared to placebo.
Secondary outcome
To investigate the pharmacokinetics of selnoflast (and metabolites, as
appropriate) in plasma.
To evaluate the effect of selnoflast on neuroinflammation in brain areas as
measured by TSPO-PET [18F]-DPA-714 imaging binding.
Background summary
PD is a progressive and incurable neurodegenerative disorder affecting more
than 10 million people worldwide (Parkinson*s Disease Foundation 2019). Age is
the main risk factor for PD and this prevalence is estimated to drastically
increase in the next decades, partially due to a global rise in average life
expectancy. The etiology of PD is unknown, and the incidence seems to vary
within subgroups defined by ethnicity, genotype, or environment (Poewe et al.
2017). PD is characterized by a progressive neurodegeneration of the central
and peripheral nervous systems, with typical neuropathological features.
Growing evidence suggests that the NLRP3 inflammasome and microglial activation
may play a role in PD by promoting neuronal dysfunction and neurodegeneration
Study objective
The objective of the study is to assess the safety and tolerability, and to
characterize the pharmacokinetics (PK) and pharmacodynamics (e.g.,
Cerebrospinal fluid [CSF] levels of IL-1β, TSPO positron emission tomography
[PET] imaging) of selnoflast administered orally to participants with early PD.
Study design
A Phase 1b, Adaptive, Multi-Center, Randomized, Double Blind,
Placebo-Controlled, Parallel Design Study.
The trial will compare daily administrations of selnoflast with matching
placebo in participants with early PD.
Intervention
A minimum of 48 eligible participants will be randomized to either receive
selnoflast 200 mg BID or placebo in a double-blind manner in a ratio
active/placebo of 2:1.
Treatment duration will be approximately 28 days for all participants. After
the last dose of selnoflast or placebo, all participants will enter a safety
follow-up period for 14 days.
Study burden and risks
Subject undergoes a 4-week treatment period in which they have to take
medication or placebo 2x daily and keep this in a diary.
In total, the subjects will make approximately 11 visits to the research
center. Of which 2 will be at the central imaging center in Amsterdam.
The investigational product may cause side effects as described in the PIS.
Blood is also drawn at most visits. The following invasive procedures will also
be performed: Insertion of an arterial line for blood collection during
TSPO-PET (2x), DAT-Scan (1x), lumbar puncture (2x), MRI (1x)
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
*Age 40-85 years
*Diagnosis of clinically probable idiopathic PD based on MDS criteria with
bradykinesia plus one of the other cardinal signs of PD (resting tremor,
rigidity)
*A time from diagnosis of PD of at least 3 to maximum 60 months at screening
Other inclusion criteria can be found in protocol section 5.1
Exclusion criteria
*Medical history indicating a Parkinsonian syndrome other than idiopathic PD
*History of brain surgery for PD.
*Known carriers for mutations in the following genes: alpha-synuclein, LRRK2,
GBA, PRKN, PINK1, or DJ1.
*Diagnosis of dementia or another significant central nervous system (CNS)
disease other than PD; history of repeated clinically significant head injury
as judged by the Investigator; history of epilepsy or seizure disorder other
than febrile seizures as a child.
Other inclusion criteria can be found in protocol section 5.2
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 | EUCTR2021-002345-15-NL |
| CCMO | NL78759.029.21 |