The main goal of this trial is to evaluate the efficacy and safety of amlenetug for the treatment of participants with Multiple System Atrophy (MSA).
This study will consist of a screening period of 10 days up to 6 weeks, a 72-week placebo-controlled period (PCP), and will include a 72-week optional dose-blinded open-label treatment extension (OLE) period. Participants in the PCP will be randomized to amlenetug high dose, amlenetug low dose or placebo (1:1:1). All participants entering the OLE will receive amlenetug during the OLE. Participants will receive intravenous infusions approximately every 4 weeks during both the PCP and OLE.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
357
Rest of the World (RoW; All Countries Except European Union [EU] and Japan [JP]) Regional-specific Outcome Measure: Mortality-adjusted Clinical Progression
Mortality-adjusted clinical progression will be assessed by the composite endpoint modified Unified Multiple System Atrophy Rating Scale (mUMSARS) score and time-to-death (any cause).
Time frame: Baseline up to Week 72
EU and JP Regional-specific Outcome Measure: Mortality-adjusted Clinical Progression
Mortality-adjusted clinical progression will be assessed by the composite endpoint Unified Multiple System Atrophy Rating Scale (UMSARS) Total Score (TS) and time-to-death (any cause).
Time frame: Baseline up to Week 72
RoW Regional-specific Outcome Measure: Mortality-adjusted Clinical Progression
Mortality-adjusted clinical progression will be assessed by the composite endpoint UMSARS TS and time-to-death (any cause).
Time frame: Baseline up to Week 72
EU and JP Regional-specific Outcome Measure: Change from Baseline in UMSARS TS
Time frame: Baseline, Week 72
RoW Regional-specific Outcome Measure: Change from Baseline in UMSARS TS
Time frame: Baseline, Week 72
Mortality-adjusted Clinical Progression
Mortality-adjusted clinical progression will be assessed by the composite endpoint UMSARS Part I and time-to-death (any cause).
Time frame: Baseline up to Week 72
Mortality-adjusted Clinical Progression
Mortality-adjusted clinical progression will be assessed by the composite endpoint UMSARS Part II and time-to-death (any cause).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Mayo Clinic
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
University of California, San Francisco Neurosciences Clinical Research Unit
San Francisco, California, United States
CenExel Rocky Mountain Clinical Research, LLC
Englewood, Colorado, United States
Yale New Haven Health
North Haven, Connecticut, United States
Parkinson's Disease And Movement Disorder Center Of Boca Raton
Boca Raton, Florida, United States
University of Florida Norman Fixel Institute for Neurological Diseases
Gainesville, Florida, United States
Indiana Health University
Indianapolis, Indiana, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
...and 64 more locations
Time frame: Baseline up to Week 72
Change from Baseline in mUMSARS Score
Time frame: Baseline, Week 72
Change from Baseline in UMSARS Part I Score
Time frame: Baseline, Week 72
Change from Baseline in UMSARS Part II Score
Time frame: Baseline, Week 72
Change from Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score
Time frame: Baseline, Week 72
Change from Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score
Time frame: Baseline, Week 72
Change from Baseline in Observer-reported Global Impression-Severity of Illness (OGI-S) Score
Time frame: Baseline, Week 72
Change from Baseline in UMSARS Part IV Score
Time frame: Baseline, Week 72
Change from Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score
Time frame: Baseline, Week 72
Change from Baseline in UMSARS Part I Item 1: Speech Score
Time frame: Baseline, Week 72
Time to Disability
Time frame: Baseline up to Week 72
Change from Baseline in EuroQol 5-dimensions, 5-levels (EQ-5D-5L) Domain Score
Time frame: Baseline, Week 72
Change from Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score
Time frame: Baseline, Week 72
Change from Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Questionnaire Domain Scores
Time frame: Baseline, Week 72
Combined Clinical Progression and Survival Score
Time frame: Baseline, Week 72
Time from Baseline to Death (Any Cause)
Time frame: Baseline up to Week 72
Number of Participants with an Absolute Increase in mUMSARS Score of <5, <7, and <9 points
Time frame: Baseline to Week 72
Number of Participants with an Absolute Increase in UMSARS TS of <16, <21, and <26 Points
Time frame: Baseline to Week 72
Percentage Change from Baseline in Brain Volume in Brain Regions of Interest (ROIs)
Time frame: Baseline, Week 72
Area Under the Curve (AUC) of amlenetug
Time frame: Baseline up to Week 72
Maximum Observed Concentration (Cmax) of Amlenetug
Time frame: Baseline up to Week 72
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 up to Week 144
Number of Participants with Anti-amlenetug Antibodies (ADAs)
Time frame: Baseline up to Week 144