ONO-2808 for Multiple System Atrophy

Not currently recruiting at 42 trial locations

Overseen By Helpdesk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ono Pharmaceutical Co. Ltd

Disqualifiers: Pregnancy, Neurological diseases, Liver diseases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ONO-2808, a new treatment for Multiple System Atrophy (MSA), to evaluate its safety and effectiveness. MSA is a rare condition affecting the nervous system, causing symptoms such as Parkinsonism, ataxia (coordination issues), and problems with blood pressure and bladder control. The trial includes individuals diagnosed with MSA in the early stages, within the first five years of symptoms, who can walk using aids like a cane if needed. Participants will receive either the new treatment or a placebo, allowing researchers to compare results. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. Please consult with the study team for guidance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that ONO-2808 is likely to be safe for humans?

Research has shown that ONO-2808 appears safe for humans. In one study, participants tolerated all tested doses of ONO-2808 well, experiencing no severe side effects. The safety record was manageable, suggesting that any side effects were neither serious nor difficult to handle.

This study remains in an early stage, so further research is necessary to confirm these findings. However, the initial results are promising regarding safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MSA?

Most treatments for Multiple System Atrophy (MSA) focus on managing symptoms with drugs like levodopa for Parkinson-like symptoms or midodrine for blood pressure issues. But ONO-2808 is different because it targets the underlying mechanisms of the disease rather than just its symptoms. Researchers are excited about ONO-2808 as it offers a potential new mechanism of action that could slow the progression of MSA. If successful, this treatment could provide a more comprehensive approach to managing the disease, offering hope for improved quality of life for patients.

What evidence suggests that ONO-2808 might be an effective treatment for MSA?

Research has shown that ONO-2808, which participants in this trial may receive, might slow the progression of Multiple System Atrophy (MSA), a disease affecting movement and balance. In earlier studies, individuals taking ONO-2808 experienced a slower decline in their ability to perform daily activities and physical tasks, as measured by a specific scale. This suggests that ONO-2808 could help people with MSA maintain their abilities longer. While these results are promising, further research is needed to confirm its benefits. ^{1 2 6 7 8}

Who Is on the Research Team?

Project Leader

Principal Investigator

Ono Pharmaceutical Co. Ltd

Are You a Good Fit for This Trial?

This trial is for patients with Multiple System Atrophy (MSA) who can walk unassisted, have had symptoms like Parkinsonism or ataxia for no more than 5 years, and are expected to live at least another 3 years. They must be able to swallow pills and not have other serious health issues or neurological disorders besides MSA.

Inclusion Criteria

I have been diagnosed with MSA according to the latest criteria.

I can walk at least 20 steps on my own, even with a walker or cane.

Patients with an anticipated survival of at least 3 years in the opinion of the Investigator.

Exclusion Criteria

I have a liver disease or cirrhosis.

I do not have any serious health issues that could interfere with the study.

I do not have Parkinson's, dementia with Lewy bodies, or similar neurological conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of ONO-2808 or placebo to assess safety, tolerability, pharmacokinetics, and pharmacodynamics

24 weeks

Regular visits for assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ONO-2808

Trial Overview

The study tests ONO-2808 against a placebo in people with MSA. It's double-blind, meaning neither the participants nor the researchers know who gets the real drug. The goal is to check if ONO-2808 is safe and how it affects the body compared to a dummy pill.

How Is the Trial Designed?

Group I: ONO-2808 Arm Experimental Treatment 1 Intervention

Group II: Placebo Arm Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Ono Pharmaceutical Co. Ltd

Lead Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Published Research Related to This Trial

In a double-blind, placebo-controlled crossover trial involving 8 patients with multiple-system atrophy (MSA), amantadine showed a trend towards reducing motor symptoms but did not achieve statistically significant improvements compared to placebo.

The study indicates that while amantadine may have some mild effects on motor function in MSA patients, it does not provide a clinically significant antiparkinsonian benefit, highlighting the need for further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of amantadine in multiple-system atrophy. Wenning, GK.[2019]

In a 52-week study involving 708 patients with moderate to severe asthma, the combination of budesonide/formoterol showed a significantly lower rate of asthma exacerbations compared to budesonide alone, indicating improved efficacy in asthma management.

The safety profile of budesonide/formoterol was acceptable, with no significant differences in adverse events or clinical abnormalities compared to budesonide, suggesting that adding a long-acting beta(2)-adrenergic agonist (LABA) to inhaled corticosteroids (ICSs) is safe for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients. Peters, SP., Prenner, BM., Mezzanotte, WS., et al.[2022]

In a 12-month observational study involving 2539 asthma patients across eight European countries, fluticasone/formoterol was found to significantly improve asthma control, with the proportion of patients achieving controlled asthma increasing from 29.4% to 67.4%.

The safety profile of fluticasone/formoterol was consistent with previous clinical trials, with 60% of patients experiencing adverse events, but only 10.2% having events possibly related to the medication, indicating it is generally safe for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-interventional study of the safety and effectiveness of fluticasone propionate/formoterol fumarate in real-world asthma management. Backer, V., Ellery, A., Borzova, S., et al.[2019]

A cross-sectional study involving 225 patients with multiple system atrophy (MSA) utilized the unified multiple system atrophy rating scale (UMSARS) to assess the disease, highlighting the need for sensitive outcome measures for future trials.

The Japan MSA research consortium (JAMSAC) aims to conduct longitudinal studies to better understand the natural history of MSA and to develop effective therapeutic trials, emphasizing the importance of appropriate trial design and inclusion criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic trial design issues for future disease-modifying therapy of multiple system atrophy]. Ichikawa, Y., Goto, J., Nakahara, Y., et al.[2019]

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by the accumulation of aggregated alpha-synuclein in oligodendrocytes, leading to significant motor and autonomic dysfunction.

Current treatments for MSA focus on symptom management, but there is a critical need for neuroprotective or disease-modifying therapies, as the underlying mechanisms of alpha-synuclein aggregation remain poorly understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple System Atrophy - State of the Art. Laurens, B., Vergnet, S., Lopez, MC., et al.[2018]

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]

The Unified Multiple System Atrophy Rating Scale (UMSARS) has significant limitations, including a ceiling effect that makes it difficult to detect changes in disease progression, as confirmed by data from the Natural History Study of the Synucleinopathies involving ongoing assessments.

There is a pressing need to develop and validate a new clinical outcome assessment (COA) for MSA, as the current UMSARS fails to accurately reflect disease severity and is influenced by symptomatic treatments, highlighting the importance of collaboration among clinicians, industry, and patient advocacy groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limitations of the Unified Multiple System Atrophy Rating Scale as outcome measure for clinical trials and a roadmap for improvement. Palma, JA., Vernetti, PM., Perez, MA., et al.[2022]

Currently, there is no disease-modifying treatment for multiple system atrophy (MSA), so the focus is on a multidisciplinary approach to manage symptoms effectively.

The review highlights the latest treatment strategies for MSA and provides insights into ongoing randomized controlled trials aimed at finding new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic Care in Multiple System Atrophy: State of the Art. Grossauer, A., Sidoroff, V., Heim, B., et al.[2023]

In a 52-week Phase III study involving 3100 patients with moderate-to-very-severe COPD, tiotropium/olodaterol (5/5 µg) showed no increase in major adverse cardiac events or serious adverse events compared to its monocomponents, indicating its safety for older patients.

The study included a diverse age range, with 51.1% of participants under 65 and 10% aged 75 or older, demonstrating that tiotropium/olodaterol is a safe treatment option for older patients with COPD who often have multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies. Ferguson, GT., Maltais, F., Karpel, J., et al.[2021]

In a patient with Child A cirrhosis due to autoimmune hepatitis, serum levels of budesonide were found to be 13 times higher than in a matched control, indicating significantly increased systemic availability of the drug.

The study suggests that reduced hepatic metabolism, rather than portosystemic shunting, may be responsible for the serious side effects experienced by the patient, as evidenced by a lower ratio of drug metabolites to budesonide levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC. Geier, A., Gartung, C., Dietrich, CG., et al.[2019]

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 PLP-α-syn transgenic mice, treatment with ATH434 for 6 months preserved motor performance and protected against neuron loss, indicating its potential as a disease-modifying therapy for multiple system atrophy (MSA).

ATH434 treatment led to a significant reduction in α-synuclein aggregates and oligomers, increased microglial lysosomal activity, and lower iron levels in the substantia nigra, suggesting a mechanism of action that enhances α-syn clearance without increasing inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ATH434 Reduces α-Synuclein-Related Neurodegeneration in a Murine Model of Multiple System Atrophy. Heras-Garvin, A., Refolo, V., Schmidt, C., et al.[2022]

In a study of 46 patients suspected of having multiple system atrophy (MSA) in Singapore, 72% were confirmed to meet the diagnostic criteria, with a predominance of MSA-C cases and a mean age of onset at 60 years.

The study found that after 3 years, 31% of patients required assistance for walking and 17% needed a wheelchair, with these rates increasing to 45% and 30% by 5 years, indicating significant disease progression over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical characteristics of patients with multiple system atrophy in Singapore. Jamora, RD., Gupta, A., Tan, AK., et al.[2020]

In a study of 467 adults with mild-to-moderate asthma, using a single inhaler of low-dose budesonide/formoterol significantly improved morning peak expiratory flow (PEF) compared to a higher dose of budesonide alone, with increases of 16.5 L/min versus 7.3 L/min.

The combination therapy also led to a 26% reduction in the risk of asthma exacerbations and improved the number of symptom-free days and asthma-control days, while showing similar safety profiles between the two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide and formoterol in a single inhaler improves asthma control compared with increasing the dose of corticosteroid in adults with mild-to-moderate asthma. Lalloo, UG., Malolepszy, J., Kozma, D., et al.[2019]

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... MSA tended to be slower in the ONO-2808 group in terms of the clinical outcome endpoint, Unified Multiple System Atrophy Rating Scale (UMSARS).

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This is a Phase 2, double-blind, parallel-group, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy

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