Study of BHV-3241 in Participants With Multiple System Atrophy (M-STAR)

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of BHV-3241 in Subjects With Multiple System Atrophy (M-STAR Study)

The purpose of this study is to compare the efficacy of verdiperstat (BHV-3241) versus placebo in participants with Multiple System Atrophy

Study Overview

• Status: Completed
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Drug: Placebo; Drug: Verdiperstat

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 06020
    • University Clinic Innsbruck
  • Vienna
    • Wien, Vienna, Austria, 1080
      • Confraternitaet Privatklinik Josefstadt in Wien
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux, Service de Neurologie
  • Marseille Cedex 5, France, 13385
    • CHU - Hospital de la Timone
  • Rennes, France, 35033
    • Unité d'investigation clinique de Neurologie Rez-de-jardin, Bloc Hopital CHU Pontchaillou
  • Strasbourg, France, 67098
    • Hopitaux Universitaire de Strasbourg-Centre de References des Maladies Autoimmunes
  • Toulouse cedex 9, France, 31059
    • CHU Purpan
• Germany
  • Bochum, Germany, 44791
    • St. Josef - Hospital Bochum, Kardiologische Studienambulanz
  • Bonn, Germany, 53127
    • Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE)
  • Dusseldorf, Germany, 40225
    • University Hospital Duesseldorf
  • Hannover, Germany, 30625
    • CRC Core Facility Medizinische Hochschule Hannover (MHH)
  • Kassel, Germany, 34128
    • Paracelsus-Elena-Klinik
  • Kiel, Germany, 24105
    • Klinik für Neurologie - UKSH - Campus Kiel
  • Marburg, Germany, 35043
    • Universitaetsklinikum Giessen und Marburg GmbH - Parkinson-Studienzentrum, Klinik für Neurologie
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • University Hospital of Liepzig
• Italy
  • Salerno, Italy, 84100
    • A.O.U. San Giovanni di Dio e Ruggi d'Aragona
  • Milan
    • Milano, Milan, Italy, 20122
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE4 5PL
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust - Campus for Ageing and Vitality (NGH)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 80013
      • Barrow Neurological Institute
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Department of Neurosciences
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center / Neurological Services
    • Palo Alto, California, United States, 84127
      • Stanford University
    • San Francisco, California, United States, 95158
      • UCSF Memory and Aging Center
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New York, New York, United States, 10032
      • Columbia University Medical Center, Neurological Institute
    • New York, New York, United States, 10016
      • NYU School of Medicine, NYU Dysautonomia Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75231
      • Kerwin Research Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of probable or possible MSA according to consensus clinical criteria (Gilman et al 2008), including participants with MSA of either subtype (MSA-P or MSA-C).
2. Able to ambulate without the assistance of another person, defined as the ability to take at least 10 steps. Use of assistive devices (e.g., walker or cane) is allowed.
3. Anticipated survival of at least 3 years at the time of Screening, as judged by the Investigator.

Exclusion Criteria:

1. Any condition that would interfere with the participant's ability to comply with study instructions, place the participant at unacceptable risk, and/or confound the interpretation of safety or efficacy data from the study, as judged by the Investigator.
2. Diagnosis of neurological disorders, other than MSA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verdiperstat; Participants received verdiperstat 300 mg tablet orally once daily for 1 week, followed by 300 mg twice daily for 1 week, and then 600 mg twice daily for the remaining 46 weeks of the double-blind phase. Participants who completed the double-blind phase were offered the opportunity to enroll in an open-label extension (OLE) phase to continue verdiperstat 600 mg twice daily for 48 weeks.	Drug: Verdiperstat; 300mg 2 oral tablets, twice daily
Placebo Comparator: Placebo; Participants received placebo matching with verdiperstat for 48 weeks. Participants who completed the double-blind phase were offered the opportunity to enroll in an OLE phase to receive verdiperstat 600 mg tablet orally twice daily for 48 weeks.	Drug: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Modified UMSARS Score at Week 48	UMSARS - clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination), Part IV (Global Disability Scale). Modified UMSARS is composed of subset of 9 items from original UMSARS Part I and Part II. Responses are measured on 4-point scale ranged from 0-3, where 0= no/mild impairment, 1= moderate impairment, 2= severe impairment, 3=complete impairment. Total modified UMSARS score is sum of these 9 items, score range from 0 to 27. Higher scores indicate greater impairment.	Baseline and Week 48
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is defined as any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received study drug; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, or, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the other serious outcomes.	Up to 100 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression of Improvement (CGI-I) Score at Week 48	The CGI-I is a clinician-rated scale measuring the change in the participant's clinical status from a specific point in time. It is scored on a 7- point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change. Higher scores indicate greater impairment.	Week 48
Change From Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Motor Subscale at Week 48	The MSA-QoL is a participant-rated scale that was designed to measure health-related quality of life specifically in MSA. It assesses activities of daily living and has subscales for motor, nonmotor, and emotional/social domains. The MSA-QoL motor subscale includes 14 items. The response to each question ranges from 0= no problem, to 4= extreme problem, with a total scale ranging from 0-56. Higher scores indicates higher impact of the disease on the aspect measured by each subscale.	Baseline and Week 48
Change From Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Non-motor Subscale at Week 48	The MSA-QoL is a participant-rated scale that was designed to measure health-related quality of life specifically in MSA. It assesses activities of daily living and has subscales for motor, nonmotor, and emotional/social domains. The MSA-QoL nonmotor subscale includes 12 items. The response to each question ranges from 0= no problem, to 4= extreme problem, with a total scale ranging from 0-48. Higher scores indicates higher impact of the disease on the aspect measured by each subscale.	Baseline and Week 48
Change From Baseline in UMSARS Part I and Part II Total Score at Week 48	The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review with 12 questions), Part II (Motor Examination with 14 questions), Part III (Autonomic Examination), and Part IV (Global Disability Scale). UMSARS Part I and Part II responses are measured on a 5-point scale ranging from 0 to 4, where 0= no impairment, 1= mild impairment, 2= moderate impairment, 3= severe impairment, 4=complete impairment. Each subscale score is a sum of its items and total score is sum of all 26 items, score range from 0 to 104. Higher scores indicates greater impairment.	Baseline and Week 48
Change From Baseline in Patient Global Impression of Severity (PGI-S) at Week 48	The PGI-S is a participant-rated scale that measures how participants perceive the severity of their illness. The PGI-S is a 1-item questionnaire on a 4-point scale ranging from 1 to 4, where, 1 = normal, 2 = mild, 3 = moderate, 4 = severe. Higher scores indicate greater impairment.	Baseline and Week 48
Change From Baseline in Clinical Global Impression of Severity (CGI-S) at Week 48	The CGI-S is a clinician-rated scale measuring the severity of the participant's illness. It is scored on a 7- point scale ranging from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). Higher scores indicate greater impairment.	Baseline and Week 48
Change From Baseline in UMSARS Part III at Week 48 (Blood Pressure (BP) Only)	The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination) and Part IV (Global Disability Scale). Only Part III of UMSARS was analyzed. Part III of the UMSARS is an Autonomic Exam, consisting of Supine and Standing Systolic and Diastolic Blood Pressure, Heart rate and presence Orthostatic Symptoms. Only change in Orthostatic Blood Pressure reported.	Baseline and Week 48
Change From Baseline in UMSARS Part III at Week 48 (Heart Rate (HR) Only)	The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination) and Part IV (Global Disability Scale). Only Part III of UMSARS was analyzed. Part III of the UMSARS is an Autonomic Exam, consisting of Supine and Standing Systolic and Diastolic Blood Pressure, Heart rate and presence Orthostatic Symptoms. Only change in Orthostatic Heart Rate reported.	Baseline and Week 48
Change From Baseline in UMSARS Part IV at Week 48	The UMSARS is a clinician-rated scale comprised of 4 parts: Part I (Historical Review), Part II (Motor Examination), Part III (Autonomic Examination) and Part IV (Global Disability Scale). Only Part IV of UMSARS was analyzed. Part IV was measured on a 5-point scale ranging from 1= Completely independent. Able to do all chores with minimal difficulty or impairment. Essentially normal. Unaware of any difficulty, to 5= Totally dependent and helpless. Bedridden. Higher scores indicate greater impairment.	Baseline and Week 48

Collaborators and Investigators

• Sponsor: Biohaven Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Schmahmann JD, Pierce S, MacMore J, L'Italien GJ. Development and Validation of a Patient-Reported Outcome Measure of Ataxia. Mov Disord. 2021 Oct;36(10):2367-2377. doi: 10.1002/mds.28670. Epub 2021 Jun 11.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Actual): July 29, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Multiple System Atrophy (MSA)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome
• Other Study ID Numbers: BHV3241-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No