Clinical trial NCT05104476: A Study of Lu AF82422 in Participants With Multiple System Atrophy
Official title: Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multi-centre Study to Assess the Efficacy, Safety and Tolerability of Lu AF82422 in Patients With Multiple System Atrophy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple System Atrophy
Keywords: Multiple System Atrophy
Neurodegenerative Disorder
Autonomic Failure
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2021-11-03
Enrollment: 64
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: To find out the effect of Lu AF82422 on disease progression in participants with multiple system atrophy.

Detailed description: This study will consist of a double-blind period (DBP) and will include an optional open-label treatment extension (OLE) period. Participants in the DBP will be randomized to Lu AF82422 or placebo (2:1). All participants entering the OLE will receive Lu AF82422 during the OLE.

Eligibility criteria: Key Inclusion Criteria:

* The participant is diagnosed with possible or probable MSA of the multiple system atrophy parkinsonian type (MSA-P) or multiple system atrophy cerebellar type (MSA-C) sub-type at the Screening Visit.
* The participant had onset of motor and/or autonomic (orthostatic or urinary) MSA symptoms within 5 years prior to the Screening Visit in the judgement of the investigator.
* The participant has an UMSARS Part I score ≤16 (omitting item 11 on sexual function) at the Screening Visit.
* The participant has a cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) with a score ≥22 at the Screening Visit.

Open-label Extension Entry Criteria

* The participant has completed the EoT Visit and did not withdraw in the DBP.
* The participant has consented to participate in the OLE.
* The participant has completed the DBP within the last 5 months and will be enrolled into the OLE no later than end of Q1 2024.
* The participant is, in the Investigator's opinion, likely to comply with the protocol.
* The participant has not received any other Investigational product since the EOoTDBP Visit.

Key Exclusion Criteria:

* The participant has been treated with an anti-α-synuclein monoclonal antibody, mesenchymal stem cells or an inhibitor of α-synuclein aggregation within the last 12 months.
* The participant has any past or current treatment with an active vaccine targeting α-synuclein.
* The participant has 2 or more blood relatives with a history of MSA.
* The participant has evidence (clinically or on MRI) and/or history of any clinically significant disease or condition other than MSA (for example, serious neurological disorder, other intracranial disease, or systemic disease).
* The participant has a current diagnosis of movement disorders that could mimic MSA (for example, 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.

Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Percentage Slowing of Clinical Progression Based on Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DB Period (DBP)
timeFrame: Baseline up to Week 72
Secondary outcomes:
measure: Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DBP
timeFrame: Baseline, Weeks 48 and 72
measure: Change From Baseline in the Modified UMSARS Part I (mUMSARS) Score at the EOT DBP
timeFrame: Baseline, Weeks 48 and 72
measure: Change From Baseline in the UMSARS Part I Scores at the EOT DBP
timeFrame: Baseline, Weeks 48 and 72
measure: Change From Baseline in the UMSARS Part II Scores at the EOT DBP
timeFrame: Baseline, Weeks 48 and 72
measure: Change From Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Change From Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Change From Baseline in Observer-Reported Global Impression - Severity of Illness (OGI-S) Score at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Composite Autonomic Symptom Score Select Change (COMPASS Select Change) Total Score at Week 48 in the DBP
timeFrame: Week 48
measure: Change From Baseline in UMSARS Part IV Score at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Change From Baseline in Speech, Swallowing, Falls, and Walking, as Assessed by the UMSARS Part I Item Scores at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Change From Baseline in Number of Falls, as Assessed by the Fall Diary Periods (Weeks 44 to 48) in the DBP
timeFrame: Baseline, Weeks 44 to 48
measure: Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Score at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in Brain Volume With Ventricles, as Measured by Volumetric MRI (vMRI) at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in P-Neurofilament Light Chain (NfL) Protein Concentration at Week 48 in the DBP
timeFrame: Baseline, Week 48
measure: Lu AF82422 Plasma Concentration in the DBP
timeFrame: Weeks 0, 4, 6, 8, 12, 24, 36, 48, 60, 72, 88
measure: Lu AF82422 Cerebrospinal Fluid (CSF) Concentrations in the DBP
timeFrame: Weeks 0 and 48
measure: Lu AF82422 CSF/Plasma Concentration Ratio in the DBP
timeFrame: Weeks 0 and 48
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: The Parkinsons and Movement Disorder Institute
state: California
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Memory and Aging Center
state: California
city: Englewood
country: United States
facility: Movement Disorders Center - Colorado Neurological Institute (CNI)
state: Colorado
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: Chicago
country: United States
facility: Rush University Medical Center, Rush University Cancer Center
state: Illinois
city: Glenview
country: United States
facility: Endeavor Health - Glenbrook Hospital
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: NYU Medical Center - Dysautonomia center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - The Neurological Institute of New York
state: New York
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center - Penn State Hershey Neuroscience Institute (PSHNI)
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh
state: Pennsylvania
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Gifu City
country: Japan
facility: Gifu University Hospital
state: Gifu Prefecture
city: Sendai-shi
country: Japan
facility: National Hospital Organization Sendai Nishitaga Hospital
state: Miyagi
Study officials:
affiliation: H. Lundbeck A/S
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: