Clinical trial NCT06706622: A Trial of Lu AF82422 in Participants With Multiple System Atrophy (MSA)
Official title: Interventional, Randomized, Double-blind, Placebo-controlled, Optional Open-label Extension Trial of Lu AF82422 in Participants With Multiple System Atrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple System Atrophy
Keywords: Lu AF82422
MSA
Neurodegenerative Disorder
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2024-11-26
Enrollment: 360
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main goal of this trial is to evaluate the efficacy and safety of Lu AF82422 for the treatment of participants with Multiple System Atrophy (MSA).

Detailed description: This study will consist of a 3-6-week screening period, 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 Lu AF82422 high dose, Lu AF82422 low dose or placebo (1:1:1). All participants entering the OLE will receive Lu AF82422 during the OLE. Participants will receive intravenous infusions approximately every 4 weeks during both the PCP and OLE.

Eligibility criteria: 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 (i.e., 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 Lu AF82422.
* The participant has taken any IMP \<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' 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.

Primary outcomes:
measure: Non-European Union (EU) Regional-specific Outcome Measure: Change from Baseline in modified Unified Multiple System Atrophy Rating Scale (mUMSARS) Score
timeFrame: Baseline up to Week 72
measure: EU Regional-specific Outcome Measure: Change from Baseline in Unified Multiple System Atrophy Rating Scale (UMSARS) Total Score (TS)
timeFrame: Baseline up to Week 72
Secondary outcomes:
measure: Change from Baseline in UMSARS TS
timeFrame: Baseline up to Week 72
measure: Change from Baseline in UMSARS Part I Score
timeFrame: Baseline up to Week 72
measure: Change from Baseline in UMSARS Part II Score
timeFrame: Baseline up to Week 72
measure: Change from Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in Observer-reported Global Impression-Severity of Illness (OGI-S) Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in UMSARS Part IV Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in UMSARS Part I Item 1: Speech Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in EuroQol 5-dimensions, 5-levels (EQ-5D-5L) Domain Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score
timeFrame: Baseline, Week 72
measure: Change from Baseline in Multiple System Atrophy Quality of Life (MSA-QoL) Questionnaire Domain Scores
timeFrame: Baseline, Week 72
measure: Combined Clinical Progression and Survival Score
timeFrame: Baseline, Week 72
measure: Time from Baseline to Death (Any Cause)
timeFrame: Baseline up to Week 72
measure: Number of Participants with an Absolute Increase in mUMSARS Score of <5, <7, and <9 points
timeFrame: Baseline, Week 72
measure: Number of Participants with an Absolute Increase in UMSARS TS of <16, <21, and <26 Points
timeFrame: Baseline, Week 72
measure: Percentage Change from Baseline in Brain Volume in Brain Regions of Interest (ROIs)
timeFrame: Baseline, Week 72
measure: Area Under the Curve (AUC) of Lu AF82422
timeFrame: Baseline up to Week 72
measure: Maximum Observed Concentration (Cmax) of Lu AF82422
timeFrame: Baseline up to Week 72
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Week 144
measure: Number of Participants with Anti-Lu AF82422 Antibodies (ADAs)
timeFrame: Baseline up to Week 144
Other outcomes:
Locations:
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research, LLC
state: Colorado
city: North Haven
country: United States
facility: Yale New Haven Health
state: Connecticut
city: Boca Raton
country: United States
facility: Parkinson's Disease And Movement Disorder Center Of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: University of Florida Norman Fixel Institute for Neurological Diseases
state: Florida
city: Indianapolis
country: United States
facility: Indiana Health University
state: Indiana
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Omaha
country: United States
facility: University Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Columbia University Medical Center - The Neurological Institute of New York
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center-Cognitive and Movement Disorders Group
state: Tennessee
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Liverpool
country: Australia
facility: Liverpool Hospital - South Western Sydney Local Health District
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin
city: Montpellier
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Saint-Eloi Guy de Chauliac
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
city: Haag in Oberbayern
country: Germany
facility: Curiositas-ad-sanum Beratungs-und Studien GmbH
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Sendai
country: Japan
facility: National Hospital Organization Sendai Nishitaga Hospital
state: Miyagi
city: Kodaira-shi
country: Japan
facility: National Center Hospital, National Center of Neurology and Psychiatry
state: Tokyo
city: Yonago-shi
country: Japan
facility: Tottori University Hospital
state: Tottori
city: Niigata
country: Japan
facility: Niigata University Medical And Dental Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Institut Clinic de Neurociencies (ICN)
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
Study officials:
affiliation: H. Lundbeck A/S
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: