Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04616456 |
| Other study ID # |
2020P003415 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
December 30, 2020 |
| Est. completion date |
January 30, 2022 |
Study information
| Verified date |
August 2022 |
| Source |
Brigham and Women's Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study will comprise of two phases, an observational phase and a treatment phase.
In the observational phase the specific aims are: 1. To determine the presence and regional
distribution of microglial activation, as assessed by 18F-PBR06 PET, in subjects with MSA as
compared to healthy controls, at baseline and at 6-9 months' follow-up.
2. To assess the relationship between microglial activation and clinical progression at
baseline and follow-up.
In the treatment phase the specific aims of the study are:
The specific aims of the study are:
1. To assess whether verdiperstat (BHV-3241) reduces 18F-PBR06 PET signal, and thus
microglial activation and inflammation, in well-characterized MSA patients.
2. To assess the relationship between PET changes and clinical progression at baseline and
follow-up in patients treated with verdiperstat.
3. To assess the relationship between PET changes and volumetric brain MRI at baseline and
follow-up in patients treated with verdiperstat.
Currently there is no known disease modifying therapy for MSA. Recently, the drug
verdiperstat (BHV-3241) has appeared in the investigational arena specifically for the
indication of Multiple System Atrophy. Verdiperstat (BHV-3241) is currently being used in a
phase 3 active drug trial at Massachusetts Hospital. Verdiperstat (BHV-3241) is known to
target Myeloperoxidase, an enzyme implicated in neuroinflammation, a major driver in disease
pathogenesis. Our previous study (IRB protocol #2016P002373) demonstrated that applying TSPO
(translator protein) PET imaging enabled us to track changes in neuroinflammation and thus
provide a viable biomarker for disease progression.
In this pilot study, the investigators aim to assess the effect of an investigational drug,
verdiperstat (BHV-3241) on microglial activation in MSA patients using [F-18]PBR06 and to
link it with clinical and morphometric MRI brain changes following treatment.
Description:
The investigators propose to use a novel TSPO PET ligand, 18F-PBR06
((18)F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline), to assess microglial
activation in MSA subjects in response to treatment with verdiperstat.16 [F-18]PBR06 is an
arlyoxyanilide-based, second generation TSPO PET ligand that has been demonstrated to have
>90% specific binding to their TSPO target in monkey brain.11 It has already been used in
humans in dosimetry studies17 and for studies assessing its pharmacokinetic and imaging
characteristics in humans16 but has never before been used in MSA subjects until our previous
study, IRB protocol #2016P002373. This study will provide a unique opportunity to assess the
utility of a novel TSPO PET ligand that has a longer radioisotope half life (approximately,
110 minutes) and hence, has the potential for widespread use depending upon the results of
this study. Assessing clinical response in chronic neurodegenerative diseases can be
challenging and objective biomarkers are urgently needed. This study would provide pilot data
to inform future potential studies using [F-18]PBR06-PET for assessing prognostication,
treatment response and drug development for MSA subjects.The investigators intend to recruit
MSA patients, one subset for whom the investigators know the longitudinal trajectory of
microglial activation changes because of prior participation in IRB protocol # 2016P002373.
This will allow us to compare the effects of verdiperstat (BHV-3241) in a well characterized
population with each patient serving as his/her own control. To be clear, patients who were
not a part of the IRB protocol #2016P002373 will also be offered the study.
The investigators intend to recruit MSA patients in whom the longitudinal trajectory of
microglial activation changes has already been determined in IRB protocol # 2016P002373. This
will allow us to compare the effects of verdiperstat (BHV-3241) in a well characterized
population with each patient serving as his/her own control. However, patients who were not a
part of the IRB protocol #2016P002373 will also be offered the study.
The investigators will recruit 8 MSA subjects with previously completed [F-18]PBR06 PET
imaging (for protocol #2016P002373) to participate in the study.
The investigators intend to include patients with probable MSA as defined by the following
criteria:
- Autonomic failure involving urinary incontinence (inability to control the release of
urine form the bladder, with erectile dysfunction in males) or an orthostatic decrease
of blood pressure within 3 min of standing by at least 30 mmHg systolic or 15 mm Hg
diastolic and
- Poorly levodopa-responsive Parkinsonism (bradykinesia with rigidity, tremor, or postural
instability) or
- A cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or
cerebellar oculomotor dysfunction) Subjects will be recruited during routine clinical
appointments by their physician or one of the other co-investigators listed on the
protocol at the Movement Disorders Clinic, 60 Fenwood Road, Boston, MA. All established
MSA patients of the Movement Disorders Clinic will be sent a letter describing the study
and a copy of the consent form.
