Effect of Verdiperstat on Microglial Activation in Well-characterized MSA Patients

NCT04616456 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 2020P003415
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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. 1.To assess whether verdiperstat (BHV-3241) reduces 18F-PBR06 PET signal, and thus microglial activation and inflammation, in well-characterized MSA patients.
2. 2.To assess the relationship between PET changes and clinical progression at baseline and follow-up in patients treated with verdiperstat.
3. 3.To assess the relationship between PET changes and volumetric brain MRI at baseline and follow-up in patients treated with verdiperstat.

Conditions

Multiple System Atrophy; Multiple System Atrophy, Cerebellar Variant; Multiple System Atrophy, Parkinson Variant (Disorder); Multiple System Atrophy (MSA) With Orthostatic Hypotension

Outcome Measures

Primary Outcomes (2)

• standardized uptake values (SUV)

  PET imaging measurement calculated over whole brain within putamen, pons, cerebellum

  1 month

• standardized uptake ratios (SUVRs)

  PET imaging measurement calculated over whole brain within putamen, pons, cerebellum

  1 month

Study Arms (1)

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.

Drug: [F-18]PBR06; Drug: Verdiperstat

Interventions

[F-18]PBR06 DRUG

PET radiopharmaceutical

Also known as: [18-F]PBR06

Multiple System Atrophy (MSA)

Verdiperstat DRUG

verdiperstat targets microglial inflammation in the brain

Also known as: BHV-3241

Multiple System Atrophy (MSA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• \. 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
• 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)

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Biohaven Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Movement Disorders Clinic, 60 Fenwood Road

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Multiple System Atrophy; Multiple system atrophy (MSA) with orthostatic hypotension

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Vikram Khurana, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Tarun Singhal, MD

  Brigham and Women's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: November 5, 2020
• Study Start: December 30, 2020
• Primary Completion: January 30, 2022
• Study Completion: January 30, 2022
• Last Updated: August 19, 2022

Record last verified: 2022-08

Locations

US (1)