Multiple System Atrophy
Conditions
Keywords
Lu AF82422, MSA, Neurodegenerative Disorder
Brief summary
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).
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.
Interventions
DRUGAmlenetug
Solution for infusion
DRUGPlacebo
Commercially available saline solution
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion 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 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rest of the World (RoW; All Countries Except European Union [EU] and Japan [JP]) Regional-specific Outcome Measure: Mortality-adjusted Clinical Progression | Baseline up to Week 72 | 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). |
| EU and JP Regional-specific Outcome Measure: Mortality-adjusted Clinical Progression | Baseline up to Week 72 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RoW Regional-specific Outcome Measure: Mortality-adjusted Clinical Progression | Baseline up to Week 72 | Mortality-adjusted clinical progression will be assessed by the composite endpoint UMSARS TS and time-to-death (any cause). |
| 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 | Baseline up to Week 72 | Mortality-adjusted clinical progression will be assessed by the composite endpoint UMSARS Part I and time-to-death (any cause). |
| 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 | — |
| 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 | — |
| Time to Disability | Baseline up to 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 | — |
| 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 | — |
| Percentage Change from Baseline in Brain Volume in Brain Regions of Interest (ROIs) | Baseline, 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 Treatment-emergent Adverse Events (TEAEs) | Day 1 up to Week 144 | — |
| Number of Participants with Anti-amlenetug Antibodies (ADAs) | Baseline up to Week 144 | — |
Countries
Australia, Canada, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTOREmail contact via H. Lundbeck A/S
H. Lundbeck A/S
Outcome results
None listed