AMX0035 for Progressive Supranuclear Palsy

(ORION Trial)

Not currently recruiting at 70 trial locations

Overseen By The Harte Group

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Amylyx Pharmaceuticals Inc.

Disqualifiers: Neurological disorders, Schizophrenia, Bipolar, Depression, others

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

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called AMX0035 (also known as Relyvrio or Albrioza) to determine its effectiveness for people with Progressive Supranuclear Palsy (PSP), a brain disorder affecting movement, balance, and eye movements. Participants will receive either the drug or a placebo (a harmless pill with no active ingredients) to compare effects. This trial targets individuals who have experienced PSP symptoms for less than 5 years and can still walk with little or no assistance. The goal is to assess whether AMX0035 can improve symptoms and is safe to use. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more information.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that AMX0035 is likely to be safe for humans?

Research has shown that AMX0035 is generally safe and well-tolerated. Previous studies found that any unwanted effects from AMX0035 were mild or moderate, meaning they were not serious. No severe side effects were reported. These results align with earlier research on AMX0035, which consistently showed similar safety outcomes. This treatment is being tested for Progressive Supranuclear Palsy (PSP) and has also been studied in other conditions with positive safety results. ^{1 2 3 4 5}

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

Most treatments for Progressive Supranuclear Palsy (PSP) focus on managing symptoms rather than altering the disease course. However, AMX0035 is unique because it targets the underlying mechanisms of neurodegeneration, potentially slowing the progression of the disease. This experimental treatment combines two active ingredients, sodium phenylbutyrate and taurursodiol, which work together to protect neurons and enhance cell survival. Researchers are excited about AMX0035 because it offers a novel approach that could provide more than just symptomatic relief, potentially improving the quality of life for individuals with PSP.

What evidence suggests that AMX0035 might be an effective treatment for Progressive Supranuclear Palsy?

In this trial, participants will receive either AMX0035 or a placebo. Research has shown that AMX0035 did not outperform a placebo in improving symptoms of Progressive Supranuclear Palsy (PSP) after 24 weeks, failing to meet the main goals set in earlier studies. However, some evidence suggests that using AMX0035 for a longer duration might stabilize or improve other conditions, such as Wolfram Syndrome.

For PSP, current data do not strongly support its effectiveness. Most participants tolerate the treatment well, experiencing no serious side effects. Consider this information when deciding to join a clinical trial for AMX0035. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Amylyx Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people aged 40-80 with Progressive Supranuclear Palsy (PSP) who've had symptoms for less than 5 years. They must be able to walk with little help, score at least 24 on a mental state exam, and not live in skilled nursing or dementia care facilities.

Inclusion Criteria

I have been diagnosed with PSP Richardson Syndrome.

My PSP symptoms started less than 5 years ago.

You have a score lower than 40 on the Progressive Supranuclear Palsy Rating Scale.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMX0035 or placebo for 52 weeks in a double-blind, placebo-controlled phase

52 weeks

Once daily for first 2 weeks, then twice daily for remainder

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of AMX0035 treatment long-term

Long-term

Once daily for first 2 weeks, then twice daily for remainder

What Are the Treatments Tested in This Trial?

Interventions

• AMX0035
• Placebo

Trial Overview The ORION Trial tests the effectiveness and safety of AMX0035 against a placebo in PSP patients. It starts with a phase where participants are randomly assigned to get either AMX0035 or placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: AMX0035 Experimental Treatment 1 Intervention

AMX0035 administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study For participants electing to continue into the open-label phase at Week 52; AMX0035 will be administered once daily for first 2 weeks and then twice daily for remainder of open-label phase

Group II: Placebo Placebo Group 1 Intervention

Placebo administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study

AMX0035 is already approved in United States, Canada for the following indications:

Approved in United States as Relyvrio for:

• Amyotrophic Lateral Sclerosis

Approved in Canada as Albrioza for:

• Amyotrophic Lateral Sclerosis

Who Is Running the Clinical Trial?

Amylyx Pharmaceuticals Inc.

Lead Sponsor

Trials

12

Recruited

1,600+

Published Research Related to This Trial

In a study involving 187 patients with progressive supranuclear palsy (PSP), the PSP-Rating Scale was identified as the most efficient measure for detecting significant changes in disease progression, requiring only 51 patients per group for a 50% change over one year.

The study found no detectable placebo effect on the PSP-Rating Scale or the Schwab and England Activities of Daily Living, suggesting that these scales can reliably assess treatment efficacy in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy. Stamelou, M., Schöpe, J., Wagenpfeil, S., et al.[2021]

A new quantitative MRI analysis method was developed to measure disease progression in progressive supranuclear palsy (PSP), using data from 99 patients in two clinical trials, which can help in designing future studies.

The study identified that changes in the volumes of the third ventricle, midbrain, and frontal lobe are effective indicators of disease progression, requiring fewer patients to detect treatment efficacy compared to traditional clinical scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. Höglinger, GU., Schöpe, J., Stamelou, M., et al.[2018]

In a study of 415 patients with parkinsonism, only 16 (3.9%) were diagnosed with progressive supranuclear palsy (PSP), highlighting the rarity of this condition.

Dopamine agonists like bromocriptine and pergolide showed improvement in 9 out of 14 trials, suggesting they may be effective treatment options for some PSP patients, especially those who did not respond to other dopaminergic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressive supranuclear palsy: clinical features and response to treatment in 16 patients. Jackson, JA., Jankovic, J., Ford, J.[2013]

Relyvrio (sodium phenylbutyrate-taurursodiol) has been approved for treating amyotrophic lateral sclerosis (ALS) based on data from a small phase 2 trial, which showed that it slowed the loss of functioning compared to a placebo.

The drug carries risks for patients sensitive to salt intake and those with disorders related to the pancreas, intestines, or enterohepatic circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Approved For ALS. Aschenbrenner, DS.[2022]

In a study involving 767 patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), riluzole did not show a significant effect on survival or disease progression compared to placebo over a median follow-up of 1095 days.

The NNIPPS diagnostic criteria demonstrated excellent validity in accurately diagnosing PSP and MSA, which can aid in early research and treatment strategies for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Bensimon, G., Ludolph, A., Agid, Y., et al.[2022]

In the CENTAUR trial, coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) significantly reduced the risk of key events such as death, tracheostomy, or permanent assisted ventilation by 47% compared to placebo, indicating its efficacy in prolonging survival in ALS patients.

PB/TURSO also delayed the first hospitalization in ALS patients, with a 44% lower risk compared to those on placebo, suggesting it may improve overall patient management and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. Paganoni, S., Hendrix, S., Dickson, SP., et al.[2023]

The coformulation of sodium phenylbutyrate and ursodoxicoltaurine (ALBRIOZA™) received conditional approval in Canada for treating amyotrophic lateral sclerosis (ALS) based on the results of the phase II CENTAUR trial.

In the CENTAUR trial, sodium phenylbutyrate/ursodoxicoltaurine demonstrated a significant slowing of ALS progression compared to placebo, indicating its potential efficacy in managing this neurodegenerative disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Phenylbutyrate and Ursodoxicoltaurine: First Approval. Heo, YA.[2022]

Edaravone (Radicava) is a new neuroprotective drug specifically developed for treating amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease.

Clinical studies have shown that edaravone can slow the decline in physical function in ALS patients, suggesting it may help preserve motor neuron health and improve quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edaravone (Radicava): A Novel Neuroprotective Agent for the Treatment of Amyotrophic Lateral Sclerosis. Cruz, MP.[2020]

The NNIPPS study developed a new clinical rating scale to assess disease severity in Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), demonstrating high reliability and validity across 362 PSP and 398 MSA patients over a 3-year period.

The scale effectively correlates with survival rates and shows responsiveness to disease progression, indicating it can be a valuable tool for evaluating treatment effects in clinical studies of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale. Payan, CA., Viallet, F., Landwehrmeyer, BG., et al.[2022]

In a study of 27 patients with Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), amantadine (100 mg twice daily) showed a notable improvement in 61.5% of MSA cases and 42.9% of PSP cases, suggesting its potential efficacy in managing these conditions.

Adverse effects were reported in 23.1% of MSA cases and 28.6% of PSP cases, indicating that while amantadine can be beneficial, monitoring for side effects is important in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amantadine effectiveness in multiple system atrophy and progressive supranuclear palsy. Rajrut, AH., Uitti, RJ., Fenton, ME., et al.[2019]

In a 9-week placebo-controlled trial involving 10 patients with progressive supranuclear palsy (PSP), the cholinergic agonist RS-86 increased cholinergic activity in the central nervous system, as shown by changes in REM sleep patterns.

Despite these changes, RS-86 did not lead to improvements in motor abilities, eye movements, or cognitive performance, indicating that simply enhancing cholinergic activity may not provide significant clinical benefits for PSP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of cholinergic agonist RS-86 to improve cognition and movement in PSP despite effects on sleep. Foster, NL., Aldrich, MS., Bluemlein, L., et al.[2019]

Sodium phenylbutyrate and taurursodiol (SP + T) have been shown to slow the progression of amyotrophic lateral sclerosis (ALS), with a significant reduction in the rate of decline in functional ability compared to placebo, as evidenced by a phase II trial involving an open-label extension phase.

Patients receiving SP + T experienced a median survival benefit of 4.8 months compared to those on placebo, highlighting its potential as a new treatment option for ALS, although further phase III trials are needed to confirm its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the Treatment of Amyotrophic Lateral Sclerosis. Alqallaf, A., Cates, DW., Render, KP., et al.[2023]

Citations

1. amylyx.com amylyx.com/news/amylyx-pharmaceuticals-to-discontinue-orion-program-of-amx0035-for-progressive-supranuclear-palsy-psp

Amylyx Pharmaceuticals to Discontinue ORION Program of ... AMX0035 did not show differences compared to placebo on primary or secondary outcomes at Week 24 - AMX0035 continued to be generally ...

2. nasdaq.com nasdaq.com/press-release/amylyx-pharmaceuticals-discontinue-orion-program-amx0035-progressive-supranuclear

Amylyx Pharmaceuticals to Discontinue ORION Program of ... AMX0035 did not show differences compared to placebo on primary or secondary outcomes at Week 24. - AMX0035 continued to be generally well- ...

3. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/amylyxpsptrial

AMX0035 and Progressive Supranuclear Palsy The purpose of this study is to determine how safe and effective the investigational drug, AMX0035, is for the treatment of PSP and to determine if AMX0035 can ...

4. amylyxpsptrial.com amylyxpsptrial.com/

Homepage | AmylyxPSPTrial The ORION trial will compare AMX0035 and placebo groups across several measures that are important when treating PSP.

5. amylyx.com amylyx.com/news/amylyx-pharmaceuticals-announces-positive-long-term-results-from-phase-2-helios-clinical-trial-of-amx0035-in-people-with-wolfram-syndrome

Amylyx Pharmaceuticals Announces Positive Long-Term ... Data at Week 48 demonstrated that treatment with AMX0035 led to sustained stabilization or improvement in multiple outcomes related to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06122662

AMX0035 and Progressive Supranuclear Palsy This clinical trial is designed to demonstrate that AMX0035 is safe and tolerable, and to assess its effect on disease progression as measured by the ...

7. withpower.com withpower.com/trial/phase-3-paralysis-10-2023-927f3

AMX0035 for Progressive Supranuclear Palsy (ORION Trial) A35-009 (ORION) is a Phase 2b/3 trial to evaluate the efficacy and safety of AMX0035 in participants with Progressive Supranuclear Palsy (PSP), ...