Multiple System AtrophyEarly Phase 1NCT04616456
Effect of Verdiperstat on Microglial Activation in Well-characterized MSA Patients
A Early Phase 1 study testing [F-18]PBR06 and Verdiperstat in people with Multiple System Atrophy and Multiple System Atrophy, Cerebellar Variant, run by Brigham and Women's Hospital at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple System Atrophy, Multiple System Atrophy, Cerebellar Variant, Multiple System Atrophy, Parkinson Variant (Disorder)
- What is being tested?
- [F-18]PBR06 and Verdiperstat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Dec 2020to 30 Jan 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject Inclusion Criteria:
- 1. Probable MSA clinical diagnosis
- Subject Exclusion Criteria:
- Individuals with a known alternate neurologic disorder, previous head injury, or substance abuse.
- Individuals with bipolar disease, schizophrenia, psychotic disorder, or any severe psychiatric disorder
- History of substance abuse disorder
Show all 24Show fewer
- Concurrent medical conditions that contraindicate study procedures
- Women who are pregnant or nursing. Also, any woman who is seeking to become pregnant or suspects she is pregnant will be excluded from enrollment.
- Individuals with claustrophobia
- Non-MRI compatible implanted devices
- Individuals with a genotype indicating that they are low affinity binders of TSPO
- Abnormal thyroid function (contingent upon free T3, free T4, and TSH levels <10 mIU/L)
- Renal impairment (RI)
- Hepatic impairment (HI)
- Systemic corticosteroid treatment in the past four weeks (excluding nasal or local treatment)
- Individuals with significant cognitive impairment (i.e. MoCA score less than or equal to 20)
- Brain MRI indicative of significant abnormality (i.e. prior hemorrhage or infarct)
- Significant cardiac events within the past year (i.e. hospitalization for congestive heart failure, myocardial infarction, or arrhythmias requiring treatment).
- Medical conditions that interfere with absorption or secretion of drugs (i.e. gastrointestinal disease)
- Individuals diagnosed with Human Immunodeficiency Virus Infection Diagnosis (HIV +)
- Any other clinically significant diagnosis that is currently unstable
- Hematologic or solid malignancy diagnosis within the past 5 years
- Medical procedure or surgery within four weeks prior to screening
- Current treatment through use of any other investigational agent, dopamine antagonists, CYP1A2 inhibitors or inducers, CYP3A4 inhibitors or inducers, or CYP2B6 or CYP3A4 metabolized drugs
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Movement Disorders Clinic, 60 Fenwood Road
Boston, Massachusetts, 02115
About this study
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.
Read more
- 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:
- To assess whether verdiperstat (BHV-3241) reduces 18F-PBR06 PET signal, and thus microglial activation and inflammation, in well-characterized MSA patients.
- To assess the relationship between PET changes and clinical progression at baseline and follow-up in patients treated with verdiperstat.
- 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.
Read the detailed 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.
- Conditions
- Multiple System Atrophy, Multiple System Atrophy, Cerebellar Variant, Multiple System Atrophy, Parkinson Variant (Disorder), Multiple System Atrophy (MSA) With Orthostatic Hypotension
- Being tested
- [F-18]PBR06, Verdiperstat
- Medical subject headings
- Multiple System Atrophy, Multiple system atrophy (MSA) with orthostatic hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[F-18]PBR06Drug
Also called [18-F]PBR06
PET radiopharmaceutical
VerdiperstatDrug
Also called BHV-3241
verdiperstat targets microglial inflammation in the brain
| Study group | Role | What they receive |
|---|---|---|
| Multiple System Atrophy (MSA) | Experimental | Twenty to twenty-five subjects with probable MSA diagnosis will be recruited for this study. Each subject will undergo an [F-18]PBR06 PET and MRI scan at baseline, and will receive the experimental drug, verdiperstat (BHV-3241) under supervision of clinic staff. A follow-up [F-18]PBR06 PET and MRI scan will be performed after 6 months (26 weeks) of taking verdiperstat. Receives: Drug: [F-18]PBR06; Drug: Verdiperstat |
What is being measured
The primary outcome is the main question the study is designed to answer.
standardized uptake values (SUV)
PET imaging measurement calculated over whole brain within putamen, pons, cerebellum
Measured: 1 month
standardized uptake ratios (SUVRs)
PET imaging measurement calculated over whole brain within putamen, pons, cerebellum
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2020
- Study start30 Dec 2020
- Primary completion30 Jan 2022
- Study completion30 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Biohaven Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Vikram Khurana, MD PhD, Brigham and Women's Hospital
- Investigators
- Vikram Khurana, MD, PhD, Principal investigator, Brigham and Women's HospitalTarun Singhal, MD, Study director, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04616456
- Sponsor's protocol ID
- 2020P003415
- Status last verified
- Aug 2022
- First submitted
- 26 Oct 2020
- Last updated
- 19 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Verdiperstat on Microglial Activation in Well-characterized MSA Patients
- ClinicalTrials.gov ID
- NCT04616456
- Acronym / sponsor ID
- 2020P003415
- Conditions
- Multiple System Atrophy, Multiple System Atrophy, Cerebellar Variant, Multiple System Atrophy, Parkinson Variant (Disorder), Multiple System Atrophy (MSA) With Orthostatic Hypotension
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Biohaven Pharmaceuticals, Inc.
- Study start
- 30 Dec 2020 (actual)
- Primary completion
- 30 Jan 2022 (actual)
- Study completion
- 30 Jan 2022 (actual)
- First posted
- 5 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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:
- To assess whether verdiperstat (BHV-3241) reduces 18F-PBR06 PET signal, and thus microglial activation and inflammation, in well-characterized MSA patients.
- To assess the relationship between PET changes and clinical progression at baseline and follow-up in patients treated with verdiperstat.
- 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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple System Atrophy (MSA) | Experimental | Drug: [F-18]PBR06, Drug: VerdiperstatTwenty to twenty-five subjects with probable MSA diagnosis will be recruited for this study. Each subject will undergo an [F-18]PBR06 PET and MRI scan at baseline, and will receive the experimental drug, verdiperstat (BHV-3241) under supervision of clinic staff. A follow-up [F-18]PBR06 PET and MRI scan will be performed after 6 months (26 weeks) of taking verdiperstat. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 1. Probable MSA clinical diagnosis
- Individuals with a known alternate neurologic disorder, previous head injury, or substance abuse.
- Individuals with bipolar disease, schizophrenia, psychotic disorder, or any severe psychiatric disorder
- History of substance abuse disorder
- Concurrent medical conditions that contraindicate study procedures
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [F-18]PBR06Also: [18-F]PBR06PET radiopharmaceutical | Drug | Multiple System Atrophy (MSA) |
| VerdiperstatAlso: BHV-3241verdiperstat targets microglial inflammation in the brain | Drug | Multiple System Atrophy (MSA) |
Primary outcome
standardized uptake values (SUV)
Time frame: 1 month
PET imaging measurement calculated over whole brain within putamen, pons, cerebellum
standardized uptake ratios (SUVRs)
Time frame: 1 month
PET imaging measurement calculated over whole brain within putamen, pons, cerebellum
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vikram Khurana, MD, PhD principal investigator
Brigham and Women's Hospital
Tarun Singhal, MD study director
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [F-18]PBR06 and Verdiperstat in people with Multiple System Atrophy and Multiple System Atrophy, Cerebellar Variant, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
standardized uptake values (SUV) (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2022.