Lu AF82422 for Multiple System Atrophy

(AMULET Trial)

Not currently recruiting at 31 trial locations

Overseen By Email contact via H. Lundbeck A/S

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lundbeck A/S

Must not be taking: Anti-α-synuclein, Mesenchymal stem

Disqualifiers: Serious neurological disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Lu AF82422 to determine if it can slow the progression of multiple system atrophy (MSA), a rare condition affecting movement and bodily functions. Participants will receive either the treatment or a placebo (a substance with no active drug) through an infusion every four weeks for up to 72 weeks. The trial aims to better understand the treatment's effects on the disease. Ideal candidates for this trial are those diagnosed with MSA within the last five years, experiencing movement or bodily function issues, but without other significant neurological conditions. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have been treated with certain medications like anti-α-synuclein monoclonal antibodies or mesenchymal stem cells in the last 12 months.

Is there any evidence suggesting that Lu AF82422 is likely to be safe for humans?

Research has shown that Lu AF82422 has been well tolerated in previous studies. In one study, single doses of Lu AF82422 caused no serious side effects. Another study found the treatment generally safe, with no major problems reported. Some patients even experienced positive effects, with their condition progressing more slowly. These findings suggest that Lu AF82422 could be a safe option for those considering this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple system atrophy?

Unlike the standard treatments for Multiple System Atrophy, which primarily focus on managing symptoms with medications like levodopa or autonomic drugs, Lu AF82422 offers a novel approach. Lu AF82422 is an antibody treatment that specifically targets misfolded proteins, which are believed to play a key role in the progression of this disease. This targeted mechanism of action is what sets it apart and has researchers excited about its potential to modify the disease process itself, rather than just alleviating symptoms. Additionally, its administration via intravenous infusion every four weeks could provide a consistent therapeutic effect, potentially leading to longer-term benefits for patients.

What evidence suggests that Lu AF82422 might be an effective treatment for multiple system atrophy?

Studies have shown that Lu AF82422 might help slow the progression of multiple system atrophy (MSA), a condition affecting movement and balance. Research suggests this treatment targets a protein called alpha-synuclein, believed to be involved in the disease. Early results indicate that Lu AF82422 is generally well tolerated and may work better in patients with milder symptoms. In this trial, some participants will receive Lu AF82422, while others will receive a placebo. Specifically, patients taking Lu AF82422 experienced slower disease progression compared to those on a placebo. Overall, the treatment appears promising for managing MSA symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Email contact via H. Lundbeck A/S

Principal Investigator

H. Lundbeck A/S

Are You a Good Fit for This Trial?

This trial is for individuals with multiple system atrophy (MSA) diagnosed within the last 5 years, having motor or autonomic symptoms. They should have a UMSARS Part I score ≤16 and a MoCA score ≥22, indicating certain levels of physical and cognitive function. Participants must be likely to follow the study protocol and not have used other investigational products recently.

Inclusion Criteria

Your UMSARS Part I score is less than or equal to 16, excluding the item about sexual function.

The participant has not received any other Investigational product since the EOoTDBP Visit.

The participant is, in the Investigator's opinion, likely to comply with the protocol.

Exclusion Criteria

I have not been treated with specific Parkinson's disease therapies in the last year.

I have been diagnosed with a movement disorder other than MSA.

I have no significant health issues other than MSA.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Period (DBP)

Participants are randomized to receive either Lu AF82422 or placebo via IV infusion every 4 weeks

48-72 weeks

IV infusion every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension (OLE)

Participants may opt into continuation of treatment with Lu AF82422 IV infusion

Up to 92 weeks

IV infusion starting on Day 1 of the OLE

What Are the Treatments Tested in This Trial?

Interventions

• Lu AF82422
• Placebo

Trial Overview The study tests Lu AF82422's effect on disease progression in MSA patients against a placebo. It aims to understand if this drug can slow down the worsening of symptoms associated with MSA, which includes both parkinsonian (MSA-P) and cerebellar types (MSA-C).

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

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.

Group II: Lu AF82422 Experimental Treatment 1 Intervention

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 188.

Lu AF82422 is already approved in United States, European Union, Japan, China for the following indications:

Approved in United States as Lu AF82422 for:

• None approved yet; in Phase III trials for Multiple System Atrophy

Approved in European Union as Lu AF82422 for:

• None approved yet; granted Orphan Drug Designation for Multiple System Atrophy

Approved in Japan as Lu AF82422 for:

• None approved yet; in Phase III trials for Multiple System Atrophy

Approved in China as Lu AF82422 for:

• None approved yet; in Phase I trials for Multiple System Atrophy

Who Is Running the Clinical Trial?

H. Lundbeck A/S

Lead Sponsor

Trials

332

Recruited

78,300+

Charl van Zyl

H. Lundbeck A/S

Chief Executive Officer since 2023

Degree in Medical Biochemistry from the University of Cape Town, South Africa

Johan Luthman

H. Lundbeck A/S

Chief Medical Officer since 2019

MD from the University of Gothenburg, Sweden

Published Research Related to This Trial

Multiple system atrophy (MSA) is a severe neurodegenerative disorder with a mean survival of only 9 years, characterized by autonomic failure and either parkinsonism or cerebellar ataxia, with limited treatment options available.

While pharmacological treatments for motor symptoms are largely ineffective, early identification and treatment of autonomic and urogenital symptoms can be beneficial, and ongoing multicenter trials are exploring potential neuroprotective therapies like riluzole and human recombinant growth hormone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple system atrophy: an update. Wenning, GK., Geser, F., Stampfer-Kountchev, M., et al.[2013]

An international meeting in 2014 brought together experts to identify key research areas for improving understanding and treatment of multiple system atrophy (MSA), a rare neurodegenerative disorder.

Eight critical topics were established, including pathogenesis, clinical measures, and treatment designs, with expert-led working groups creating prioritized recommendations to guide future research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. Walsh, RR., Krismer, F., Galpern, WR., et al.[2021]

In a study involving 18 patients with multiple system atrophy (MSA), 8 patients with Parkinson's disease (PD), and 10 healthy volunteers, it was found that MSA patients activated different brain regions compared to PD patients, particularly showing less activation in the cerebellum and more in the supplementary motor and superior parietal areas.

After an acute levodopa challenge, MSA patients showed reduced activation in the anterior cingulate, while PD patients increased activation in the right cerebellum, indicating that MSA patients do not benefit from levodopa in the same way as PD patients due to underlying cerebellar dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor activation in multiple system atrophy and Parkinson disease: a PET study. Payoux, P., Brefel-Courbon, C., Ory-Magne, F., et al.[2016]

In a placebo-controlled trial involving 10 patients with probable multiple system atrophy (MSA), riluzole (100 mg twice daily) was found to be well tolerated but did not show significant anti-Parkinsonian effects based on the Unified Parkinson's Disease Rating Scale (UPDRS).

The results suggest that riluzole is unlikely to provide clinically meaningful benefits for Parkinsonian symptoms in MSA, prompting further investigation into its potential disease-modifying effects in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of riluzole in multiple system atrophy. Seppi, K., Peralta, C., Diem-Zangerl, A., et al.[2015]

In a study of 139 patients suspected of having multiple system atrophy (MSA), [123I]Ioflupane SPECT demonstrated high sensitivity (82.46%) and positive predictive value (86.24%), making it a reliable diagnostic tool for MSA, especially effective in identifying the parkinsonian subtype (MSA-P) with a sensitivity of 97.26%.

The SPECT imaging was significantly more effective than MRI, which was normal in 89.2% of cases, highlighting its utility in distinguishing between healthy individuals and those with MSA, as well as differentiating between the MSA-P and MSA-C subtypes at the initial clinical suspicion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Effectiveness of [123I]Ioflupane Single Photon Emission Computed Tomography (SPECT) in Multiple System Atrophy. Villena-Salinas, J., Ortega-Lozano, SJ., Amrani-Raissouni, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05104476

NCT05104476 | A Study of Lu AF82422 in Participants ... Reported here is the estimated slowing (%) of clinical progression in participants receiving Lu AF82422 relative to those receiving placebo. UMSARS is a ...

2. neurologylive.com neurologylive.com/view/a-synuclein-antibody-lu-af82422-disease-modifying-potential-phase-2-amulet-trial-msa

A-Synuclein Antibody Lu AF82422 Shows Disease ... Lu AF84222 was considered well tolerated, with greater treatment effects observed in a subgroup of patients with less impaired multiple system atrophy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06706622

A Trial of Lu AF82422 in Participants With Multiple System ... 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).

4. nature.com nature.com/articles/s41531-024-00849-1

Rational selection of the monoclonal α-synuclein antibody ... The data supporting Lu AF82422 includes structural understanding of the epitope, binding affinities, and functional effects in cellular and mice ...

5. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29784

Randomized Phase I Trial of the α‐Synuclein Antibody Lu ... The aim was to evaluate the safety, tolerability, pharmacokinetics, and target engagement of ascending doses of Lu AF82422.

6. mdsabstracts.org mdsabstracts.org/abstract/safety-and-efficacy-of-the-anti-alpha-synuclein-monoclonal-antibody-lu-af82422-for-the-treatment-of-patients-with-msa-results-from-the-phase-2-amulet-trial/

Safety and Efficacy of the Anti-alpha Synuclein Monoclonal ... Subgroup analysis in a less impaired population (Lu AF82422 n=30; placebo n=12) revealed an overall 37% slowing of clinical progression. Lu AF82422 was ...