AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy

Sponsor

H. Lundbeck A/S (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05104476

Collaborator

(none)

Enrollment

Locations

Arms

21.4

Anticipated Duration (Months)

3.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple System Atrophy	Drug: Lu AF82422 Drug: Placebo	Phase 2

Detailed Description

The participants will be randomized to Lu AF82422 or placebo (2:1).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 16, 2021

Anticipated Primary Completion Date :

May 27, 2023

Anticipated Study Completion Date :

Aug 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lu AF82422 Participants will receive Lu AF82422 intravenous (IV) infusion every 4 weeks (Q4W) from Baseline for a minimum 48 weeks up to a maximum 72 weeks.	Drug: Lu AF82422 Solution for infusion
Experimental: Placebo Participants will receive Lu AF82422 matching placebo IV infusion Q4W from Baseline for a minimum 48 weeks up to a maximum 72 weeks.	Drug: Placebo Solution for infusion

Arm

Intervention/Treatment

Experimental: Lu AF82422

Participants will receive Lu AF82422 intravenous (IV) infusion every 4 weeks (Q4W) from Baseline for a minimum 48 weeks up to a maximum 72 weeks.

Drug: Lu AF82422

Solution for infusion

Experimental: Placebo

Participants will receive Lu AF82422 matching placebo IV infusion Q4W from Baseline for a minimum 48 weeks up to a maximum 72 weeks.

Drug: Placebo

Solution for infusion

Outcome Measures

Primary Outcome Measures

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) [Baseline, EOT (Week 48 to 72)]

Secondary Outcome Measures

Change From Baseline in the Modified UMSARS Part I (mUMSARS) Score at the EOT [Baseline, EOT (Week 48 to 72)]
Change From Baseline in the UMSARS Part I and UMSARS Part II Scores at the EOT [Baseline, EOT (Week 48 to 72)]
Change From Baseline in UMSARS TS, UMSARS Part I, mUMSARS and UMSARS Part II Scores at Week 48 [Baseline, Week 48]
Change From Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score at Week 48 [Baseline, Week 48]
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 48 [Baseline, Week 48]
Change From Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score at Week 48 [Baseline, Week 48]
Change From Baseline in Observer-Reported Global Impression - Severity of Illness (OGI-S) Score at Week 48 [Baseline, Week 48]
Change From Baseline in Composite Autonomic Symptom Score Select Change (COMPASS Select Change) Score at Week 48 [Baseline, Week 48]
Change From Baseline in UMSARS Part IV Score at Week 48 [Baseline, Week 48]
Change From Baseline in Speech, Swallowing, Falls, and Walking, as Assessed by the UMSARS Part I Item Scores at Week 48 [Baseline, Week 48]
Change From Baseline in Frequency, Cause, and Consequence of Falls, as Assessed by the Fall Diary Periods at Week 48 [Baseline, Week 48]
Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Score at Week 48 [Baseline, Week 48]
Percent Change From Baseline in Brain Volume, as Measured by Volumetric MRI (vMRI) at Week 48 [Baseline, Week 48]
Change From Baseline in Neurofilament Light Chain (NfL) Concentrations at Week 48 [Baseline, Week 48]
Lu AF82422 Plasma Concentration [0 to Week 88]
Lu AF82422 Cerebrospinal Fluid (CSF) Concentrations [Weeks 48]
Lu AF82422 CSF/Plasma Concentration Ratio [Week 48]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Parkinson's and Movement Disorder Institute	Fountain Valley	California	United States	92708
2	University of California, San Diego	La Jolla	California	United States	92037
3	UCSF Memory and Aging Center	San Francisco	California	United States	94158
4	Rocky Mountain Movement Disorders Center	Englewood	Colorado	United States	80113
5	Parkinson's Disease And Movement Disorder Center Of Boca Raton	Boca Raton	Florida	United States	33486
6	University of Florida- Norman Fixel Institute for Neurological Diseases	Gainesville	Florida	United States	32608
7	Rush University Medical Center	Chicago	Illinois	United States	60612
8	NorthShore University Healthsystem Neurological Institute	Glenview	Illinois	United States	60026
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	Mayo Clinic	Rochester	Minnesota	United States	55905
11	University Nebraska Medical Center	Omaha	Nebraska	United States	68198-8440
12	NYU Medical Center - Dysautonomia center	New York	New York	United States	10016
13	Columbia University Medical Center - The Neurological Institute of New York	New York	New York	United States	10032
14	Penn State Milton S. Hershey Medical Center - Penn State Hershey Neuroscience Institute (PSHNI)	Hershey	Pennsylvania	United States	17033
15	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19107
16	University Of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
17	Fujita Health University Hospital	Toyoake	Aichi	Japan	470-1192
18	Gifu University Hospital	Gifu City	Gifu Prefecture	Japan	501-1194
19	National Hospital Organization Sendai Nishitaga Hospital	Sendai-shi	Miyagi	Japan	982-8555