A Study of Lu AF82422 in Participants With Multiple System Atrophy

Study Overview
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Brief Summary
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To find out the effect of Lu AF82422 on disease progression in participants with multiple system atrophy.

Detailed Description
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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.

Official Title
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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

Conditions
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Multiple System Atrophy

Intervention / Treatment
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* Drug: Lu AF82422
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lu AF82422<br>Participants in the DBP will receive Lu AF82422 intravenous (IV) infusion every 4 weeks (Q4W) from Baseline for a minimum 48 weeks up to a maximum 72 weeks. In the optional OLE, all participants will receive Lu AF82422 IV infusion starting on Day 1 of the OLE up to week 44. | Drug: Lu AF82422<br>* Solution for infusion<br>|
| Experimental: Placebo<br>Participants in the DBP will receive Lu AF82422 matching placebo IV infusion Q4W from Baseline for a minimum 48 weeks up to a maximum 72 weeks. | Drug: Placebo<br>* Solution for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Unified Multiple System Atrophy Rating Scale (UMSARS) Part I and Part II Total Score (UMSARS TS) at the End of Treatment (EOT) DBP |  | Baseline, EOTDBP (Week 48 to 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Modified UMSARS Part I (mUMSARS) Score at the EOT DBP |  | Baseline, EOTDBP (Week 48 to 72) | 
| Change From Baseline in the UMSARS Part I and UMSARS Part II Scores at the EOT DBP |  | Baseline, EOTDBP (Week 48 to 72) | 
| Change From Baseline in UMSARS TS, UMSARS Part I, mUMSARS and UMSARS Part II Scores at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Observer-Reported Global Impression - Severity of Illness (OGI-S) Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Composite Autonomic Symptom Score Select Change (COMPASS Select Change) Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in UMSARS Part IV Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Speech, Swallowing, Falls, and Walking, as Assessed by the UMSARS Part I Item Scores at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Frequency, Cause, and Consequence of Falls, as Assessed by the Fall Diary Periods at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Score at Week 48 in the DBP |  | Baseline, Week 48 | 
| Percent Change From Baseline in Brain Volume, as Measured by Volumetric MRI (vMRI) at Week 48 in the DBP |  | Baseline, Week 48 | 
| Change From Baseline in Neurofilament Light Chain (NfL) Concentrations at Week 48 in the DBP |  | Baseline, Week 48 | 
| Lu AF82422 Plasma Concentration |  | 0 to Week 65 of the OLE | 
| Lu AF82422 Cerebrospinal Fluid (CSF) Concentrations in the DBP |  | Weeks 48 | 
| Lu AF82422 CSF/Plasma Concentration Ratio in the DBP |  | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple System Atrophy, Neurodegenerative Disorder, Autonomic Failure