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

Phase 3

Recruiting

• Conditions: Multiple System Atrophy
• Interventions: Drug: Lu AF82422; Drug: Placebo

• Registration Number: NCT06706622
• Lead Sponsor: H. Lundbeck A/S

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.

Study Timeline

• Study First Submitted: 2024-11-22
• Study First Submitted QC: 2024-11-22
• Study First Posted: 2024-11-26
• Study Start: 2024-12-03
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2028-02-17
• Study Completion: 2029-10-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lu AF82422 Low Dose	Lu AF82422	Participants will receive Lu AF82422 by intravenous infusion
Lu AF82422 High Dose	Lu AF82422	Participants will receive Lu AF82422 by intravenous infusion
Placebo	Placebo	Participants will receive commercially available saline solution for infusion

Primary Outcome Measures

Name	Time	Method
Non-European Union (EU) Regional-specific Outcome Measure: Change from Baseline in modified Unified Multiple System Atrophy Rating Scale (mUMSARS) Score	Baseline up to Week 72
EU Regional-specific Outcome Measure: Change from Baseline in Unified Multiple System Atrophy Rating Scale (UMSARS) Total Score (TS)	Baseline up to Week 72

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Concentration (Cmax) of Lu AF82422	Baseline up to Week 72
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Day 1 up to Week 144
Number of Participants with Anti-Lu AF82422 Antibodies (ADAs)	Baseline up to Week 144
Percentage Change from Baseline in Brain Volume in Brain Regions of Interest (ROIs)	Baseline, Week 72
Area Under the Curve (AUC) of Lu AF82422	Baseline up to Week 72
Number of Participants with an Absolute Increase in mUMSARS Score of <5, <7, and <9 points	Baseline, Week 72
Number of Participants with an Absolute Increase in UMSARS TS of <16, <21, and <26 Points	Baseline, Week 72
Change from Baseline in UMSARS TS	Baseline up to Week 72
Change from Baseline in UMSARS Part I Score	Baseline up to Week 72
Change from Baseline in UMSARS Part II Score	Baseline up to Week 72
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

Trial Locations

Locations (4)

Parkinson's Disease And Movement Disorder Center Of Boca Raton; 🇺🇸 Boca Raton, Florida, United States

CenExel Rocky Mountain Clinical Research, LLC; 🇺🇸 Englewood, Colorado, United States

QUEST Research Institute; 🇺🇸 Farmington Hills, Michigan, United States

Inland Northwest Research; 🇺🇸 Spokane, Washington, United States