A Trial of Amlenetug (Lu AF82422) in Participants With Multiple System Atrophy (MSA) (MASCOT)

Interventional, Randomized, Double-blind, Placebo-controlled, Optional Open-label Extension Trial of Lu AF82422 in Participants With Multiple System Atrophy

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Drug: Placebo; Drug: Amlenetug

Detailed Description

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 open-label treatment extension (OLE) period. Participants in the PCP will be randomized to amlenetug or placebo. 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
• Enrollment (Actual): 401
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital - South Western Sydney Local Health District
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Gold Coast Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital (TWH)
• France
  • Bordeaux, France, 33076
    • Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire de Lille - Hopital Roger Salengro
  • Marseille, France, 13385
    • CHU - Hospital de la Timone
  • Montpellier, France, 34295
    • Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Saint-Eloi Guy de Chauliac
  • Paris, France, 75651
    • Chu De La Pitie-Salpetriere
  • Rennes, France, 35033
    • Unite d'investigation clinique de Neurologie Rez-de-jardin-Bloc Hopital CHU Pontchaillou
  • Toulouse, France, 31059
    • Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
• Germany
  • Beelitz-Heilstätten, Germany, 14547
    • Movement Disorders Clinic
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Haag in Oberbayern, Germany, 83527
    • Curiositas-ad-Sanum GmbH
  • München, Germany, 81377
    • Ludwig-Maximilians-Universitat Munchen Klinikum der Universitat - Grosshadern
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Tübingen, Germany, 72076
    • University Hospital Tuebingen
• Italy
  • Bologna, Italy, 40139
    • IRCCS Institute of Neurological Sciences of Bologna- Universita di Bologna
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
  • Naples, Italy, 80138
    • AOU Universita della Campania Luigi Vanvitelli
  • Pisa, Italy, 56126
    • A.O.U. Pisana-Ospedale S. Chiara
  • Salerno, Italy, 84100
    • Universita Di Salerno Aou San Giovanni Di Dio E Ruggi D'Aragona
• Japan
  • Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Niigata, Japan, 9518520
    • Niigata University Medical and Dental Hospital
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 465-8620
      • National Hospital Organization Higashinagoya National Hospital
    • Toyoake, Aichi-ken, Japan, 470-1192
      • Fujita Health University Hospital
  • Gifu
    • Gifu, Gifu, Japan, 501-1194
      • Gifu University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 982-8555
      • National Hospital Organization Sendai Nishitaga Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Kodaira-shi, Tokyo, Japan, 187-8551
      • National Center Hospital, National Center of Neurology and Psychiatry
  • Tottori
    • Yonago-shi, Tottori, Japan, 683-8504
      • Tottori University Hospital
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 02447
    • Kyung Hee University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona - Institut Clinic de Neurociencies (ICN)
  • Barcelona (Spain), Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28006
    • Hospital Universitario De La Princesa
  • Seville, Spain, 41015
    • Hospital Universitario Virgen del Rocio (HUVR) - Instituto de Biomedicina de Sevilla (IBIS)
  • Valencia, Spain, 46026
    • Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bu...
• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital - Royal Devon University Healthcare NHS Foundation Trust
  • London, United Kingdom, WC1N 3BG
    • The National Hospital for Neurology and Neurosurgery
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Nuffield Oxford University and Oxford University Hospital NHS Foundation Trusts-John Radcliffe Ho...
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Queen Elizabeth University Hospital - NHS Greater Glasgow & Clyde
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE4 5LP
      • Clinical Ageing Reseach Unit
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco Neurosciences Clinical Research Unit
  • Colorado
    • Englewood, Colorado, United States, 80113
      • CenExel Rocky Mountain Clinical Research, LLC
  • Connecticut
    • North Haven, Connecticut, United States, 06473
      • Yale New Haven Health
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease And Movement Disorder Center Of Boca Raton
    • Gainesville, Florida, United States, 32608
      • University of Florida Norman Fixel Institute for Neurological Diseases
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Health University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198-8440
      • University Nebraska Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Medical Center - Dysautonomia center
    • New York, New York, United States, 10032-3726
      • Columbia University Medical Center - The Neurological Institute of New York
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Neurological Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center-Cognitive and Movement Disorders Group
  • Texas
    • Dallas, Texas, United States, 75390-8565
      • University of Texas Southwestern Medical Center ¿ Multiple System Atrophy Clinic
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Washington
    • Spokane, Washington, United States, 99202
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• The participant has a diagnosis of clinically established multiple system atrophy parkinsonian type (MSA-P) or multiple system atrophy cerebellar type (MSA-C), or clinically probable MSA-P or MSA-C, according to the 2022 Movement Disorders Society (MDS) criteria for the diagnosis of MSA at the Screening Visit.
• The participant had onset of motor MSA symptoms (that is, parkinsonian and/or cerebellar) within 5 years prior to the Screening Visit in the judgement of the investigator.
• The participant has an anticipated survival of >3 years, in the opinion of the investigator, at the Screening Visit.
• The participant has suitable peripheral venous access for investigational medicinal product (IMP) administration and blood sampling.
• The participant has an UMSARS Part I score ≤16 (omitting item 11 on sexual function) at the Screening Visit.

Exclusion Criteria:

• The participant has previously been dosed with amlenetug.
• The participant has taken any active IMP within 3 months or 5 half lives of that product, whichever is longer, prior to the first dose of IMP.
• The participant has 2 or more first degree relatives with a history of MSA.
• The participant, if of MSA-P subtype, has unexplained anosmia (not explained by other common causes such as allergic rhinitis or smoking, nasal structural lesions, or nasal surgery) on olfactory testing at the Screening Visit.
• The participant has evidence (clinically or on magnetic resonance imaging (MRI)) and/or history of any clinically significant disease or condition other than MSA, that is, in the investigator's opinion, likely to affect CNS functioning, e.g., serious neurological disorder, other intracranial or systemic disease.
• The participant has a current diagnosis of movement disorders that could mimic MSA, e.g., Parkinson's disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, pharmacological, or post-encephalitic parkinsonism, per investigator discretion. Participants who have previously been incorrectly diagnosed with Parkinson's disease will not be excluded.

Other protocol-defined inclusion and exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive commercially available saline solution for infusion	Drug: Placebo; Commercially available saline solution
Experimental: Amlenetug; Participants will receive amlenetug by intravenous infusion	Drug: Amlenetug; Solution for infusion; Other Names: Lu AF82422

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	Baseline up to Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score		Baseline, Week 72
Change from Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score		Baseline, Week 72
Change from Baseline in Observer-reported Global Impression-Severity of Illness (OGI-S) Score		Baseline, Week 72
Change from Baseline in UMSARS Part IV Score		Baseline, Week 72
Change from Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score		Baseline, Week 72
Change from Baseline in UMSARS Part I Item 1: Speech Score		Baseline, Week 72
Change from Baseline in EuroQol 5-dimensions, 5-levels (EQ-5D-5L) Domain Score		Baseline, Week 72
Change from Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score		Baseline, Week 72
Change from Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Questionnaire Domain Scores		Baseline, Week 72
Combined Clinical Progression and Survival Score		Baseline, Week 72
Time from Baseline to Death (Any Cause)		Baseline up to Week 72
Percentage Change from Baseline in Brain Volume in Brain Regions of Interest (ROIs)		Baseline, Week 72
Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Day 1 up to Week 144
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).	Baseline up to Week 72
EU and JP Regional-specific Outcome Measure: Change from Baseline in UMSARS TS		Baseline, Week 72
RoW Regional-specific Outcome Measure: Change from Baseline in UMSARS TS		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).	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).	Baseline up to Week 72
Change from Baseline in mUMSARS Score		Baseline, Week 72
Change from Baseline in UMSARS Part I Score		Baseline, Week 72
Change from Baseline in UMSARS Part II Score		Baseline, Week 72
Time to Disability		Baseline up to Week 72
Number of Participants with an Absolute Increase in mUMSARS Score of <5, <7, and <9 points		Baseline to Week 72
Number of Participants with an Absolute Increase in UMSARS TS of <16, <21, and <26 Points		Baseline to Week 72
Area Under the Curve (AUC) of amlenetug		Baseline up to Week 72
Maximum Observed Concentration (Cmax) of Amlenetug		Baseline up to Week 72
Number of Participants with Anti-amlenetug Antibodies (ADAs)		Baseline up to Week 144

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Investigators: Study Director: Email contact via H. Lundbeck A/S, H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2024
• Primary Completion (Estimated): February 17, 2028
• Study Completion (Estimated): October 25, 2029

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MSA; Neurodegenerative Disorder; Lu AF82422
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Multiple System Atrophy; Neurodegenerative Diseases; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 20432A; 2024-517169-18-00 (Registry Identifier: EU CT)

Drug and device information, study documents

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