Study of BHV-3241 in Participants With Multiple System Atrophy

Multiple System Atrophy Clinical Trial

— M-STAR  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03952806
• Other study ID #: BHV3241-301
• Status: Completed
• Phase: Phase 3
• Start date: July 29, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: September 2023
• Source: Biohaven Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 421
• Est. completion date: June 30, 2022
• Est. primary completion date: July 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Shy-Drager Syndrome

Intervention

Drug:
• Verdiperstat
300mg 2 oral tablets, twice daily
• Placebo
Matching placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biohaven Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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