AzTrials
AzTrials

Progressive Supranuclear PalsyPhase 2/3ORIONNCT06122662

AMX0035 and Progressive Supranuclear Palsy

A Phase 2/3 study testing AMX0035 in people with Progressive Supranuclear Palsy and PSP, run by Amylyx Pharmaceuticals Inc. at 62 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A35-009 (ORION) is a Phase 2b/3 trial to evaluate the efficacy and safety of AMX0035 in participants with Progressive Supranuclear Palsy (PSP), consisting of randomized, double blind placebo controlled phases, followed by an optional open-label extension phase. Read more about this study

Who is it for?
Ages 40 to 80 years
What is being tested?
AMX0035
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
139 participants
Where
62 sitesin 5 countries
Study dates
21 Dec 2023to 21 Oct 2025
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female 40 to 80 years of age, inclusive
  • Diagnosis of possible or probable PSP Richardson Syndrome
  • Presence of PSP symptoms for <5 years
  • Score of <40 on the total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS)
  • Able to walk independently or with minimal assistance
  • Minimum score of 24 on the Mini Mental State Examination (MMSE)
Show all 12Show fewer
  • Must reside outside a skilled nursing facility or dementia care facility at the time of screening. Residence in an assisted living facility is allowed
  • Must have a study partner willing to attend study visits and provide information on participant's status
  • Capable of providing informed consent
  • Capable and willing to comply with trial procedures including visits to the trial clinic, visit requirements and treatment schedule, including MRI scans
  • Female participants of childbearing potential must agree to use effective birth control for the duration of the study and for 6 months after last dose of study drug.
  • Males must agree to use effective birth control method for the duration of the study and for 6 months after the last dose of study drug. Men must not plan to donate sperm.

Who cannot join

  • Require use of a feeding tube
  • Evidence of any neurological disorder that could explain signs of PSP
  • Evidence of any clinically significant neurological disorder other than PSP, including significant cerebrovascular abnormalities, vascular dementia, motor neuron disease or ALS, Huntington's disease, normal pressure hydrocephalus, brain tumor, seizure disorder, multiple sclerosis, or known structural brain abnormalities.
  • History of autosomal dominant PSP due to a Microtubule Associated Protein Tau (MAPT) mutation
  • History of an autosomal dominant mutation associated with Frontotemporal Lobar Degeneration (FTLD)
  • Prior or current diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
Show all 11Show fewer
  • Presence of unstable psychiatric disease, cognitive impairment (e.g., major cognitive dysfunction), dementia, major depression, or substance abuse that would impair ability of the participant to provide informed consent and follow instructions
  • Abnormal liver function
  • Renal insufficiency
  • Ongoing anemia
  • History of Class III/IV heart failure per New York Heart Association (NYHA)

Trial locations and contacts

62 sites in 5 countries.

62 sites in 5 countries

United States35 sites

  • Augusta University

    Augusta, Georgia, 30912

  • UC Health Anschutz Outpatient Pavilion Anschutz Medical Campus

    Aurora, Colorado, 80045

  • Parkinson's Disease and Movement Disorders Center of Boca Raton

    Boca Raton, Florida, 33486

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

  • Northwestern University PD and Movement Disorders Center

    Chicago, Illinois, 60611

  • University of Cincinnati

    Cincinnati, Ohio, 45219

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Kerwin Medical Center

    Dallas, Texas, 75231

  • Quest Research Institute

    Farmington Hills, Michigan, 48334

  • Parkinson's & Movement Disorder Institute

    Fountain Valley, California, 92708

  • UF Health Dorothy Mangurian Neuroimaging Suite

    Gainesville, Florida, 32608

  • Parkinsons and Movement Disorder Center at the Queens Medical Center

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • University of Kansas Medical Center Research Institute, Inc.

    Kansas City, Kansas, 66160

  • Cleveland Clinic Lou Ruvo Center for Brain Health

    Las Vegas, Nevada, 89106

  • University of Kentucky Medical Center

    Lexington, Kentucky, 40536-0274

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • University of Southern California

    Los Angeles, California, 90033

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Veracity Neuroscience, LLC

    Memphis, Tennessee, 38157

  • University of Minnesota, CTSI

    Minneapolis, Minnesota, 55414

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121

  • Stanford Movement Disorder Center

    Palo Alto, California, 94304

  • Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19107

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Virginia Commonwealth University Department of Neurology

    Richmond, Virginia, 23298-0059

  • Mayo Clinic - Rochester

    Rochester, Missouri, 55905

  • Central Texas Neurology Consultants

    Round Rock, Texas, 78681

  • University of Utah Movement Disorders Center

    Salt Lake City, Utah, 84108

  • University of California, San Francisco (UCSF)

    San Francisco, California, 94158

  • Mayo Clinic

    Scottsdale, Arizona, 85259

Other trials in United States

France7 sites

  • Groupe Hospitalier Pellegrin - Hôpital Pellegrin

    Bordeaux, Gironde, 30076

  • Hopital Roger Salengro - CHU Lille

    Lille, Nord, 59037

  • CHU de Limoges - Hôpital Dupuytren

    Limoges, Haute Vienne, 87042

  • Hôpital de la Timone

    Marseille, Bouches-du-Rhône, 13385

  • Hopital Caremeau

    Nîmes, Gard, 30029

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, 75013

  • CHU Rennes - Hopital Pontchaillou

    Rennes, Ille Et Vilaine, 35033

Other trials in France

Germany7 sites

  • Universitaetsklinikum Carl Gustav Carus TU Dresden

    Dresden, Saxony, 1307

  • Krankenhaus Agatharied

    Hausham, Bavaria, 83734

  • Paracelsus-Elena-Klinik Kassel

    Kassel, Hesse, 34128

  • Klinikum der Universität München

    Munich, Bavaria

  • Asklepios Fachklinikum Stadtroda

    Stadtroda, Thuringia, 7646

  • Universitaetsklinikum Duesseldorf AoeR

    Ulm, Baden-Wurttemberg, 89081

  • Universitaetsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Spain7 sites

  • Hospital de Cruces

    Barakaldo, Bizkaia, 48903

  • Hospital Clinic de Barcelona

    Barcelona, 8036

  • Hospital Universitario de La Princesa

    Madrid, 28006

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Universitari i Politecnic La Fe

    Valencia, València, 46026

Other trials in Spain

Italy6 sites

  • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

    Milan, 20122

  • Fondazione IRCCS Istituto Neurologico Carlo Besta

    Milan, 20133

  • Azienda Ospedale-Università di Padova

    Padova, 35128

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma, 168

  • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

    Roma, 185

  • Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona

    Salerno, 84131

Other trials in Italy

About this study

Official title: A Phase 2b/3 Study of the Safety and Efficacy of AMX0035 in Progressive Supranuclear Palsy (ORION)

A35-009 (ORION) is a Phase 2b/3 trial to evaluate the efficacy and safety of AMX0035 in participants with Progressive Supranuclear Palsy (PSP), consisting of randomized, double blind placebo controlled phases, followed by an optional open-label extension phase.

Read the detailed description

AMX0035 is a fixed dose combination therapy designed to reduce neuronal death through blockade of key cellular death pathways originating in the endoplasmic reticulum (ER) and mitochondria. 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 Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS) over a 52-week double-blind phase. The Phase 2b and Phase 3 study portions are planned to feature an identical design: a randomized, double-blind, placebo-controlled phase that is followed by an optional open-label extension (OLE) phase. The phase 3 portion of ORION may be initiated based on results of the phase 2b Interim Analysis and/or the Primary Analysis and the totality of data from the Phase 2b study portion.

Being tested
AMX0035, Placebo
Keywords
Progressive Supranuclear Palsy, PSP, Steele-Richardson-Olszewski Syndrome, ORION, Amylyx
Medical subject headings
Supranuclear Palsy, Progressive, Neurodegenerative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AMX0035Drug

    Proprietary formulation of sodium phenylbutyrate and taurursodiol

  • PlaceboOther

    Matching Placebo Comparator

Study groups in NCT06122662
Study groupRoleWhat they receive
AMX0035ExperimentalAMX0035 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
Receives: Drug: AMX0035
PlaceboPlacebo comparatorPlacebo administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score

    Assess the impact of AMX0035 on disease progression as measured by the Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS); Total scores range from 0-96 with higher scores indicating more progressed disease

    Measured: 52 weeks

Secondary outcomes (3)

  1. Change in total (10-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score

    Assess the impact of AMX0035 on disease progression as measured by the Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS); Total scores range from 0-30 with higher scores indicating more progressed disease

    Measured: 52 weeks

  2. Change in MDS-UPDRS Part II Score

    To evaluate the efficacy of AMX0035 on motor aspects of activities of daily living as measured on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-PDRS) Part II; Total scores range from 0-52 with lower scores indicating better function

    Measured: 52 weeks

  3. Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Safety and tolerability of AMX0035 in participants with PSP

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2023
  2. Study start21 Dec 2023
  3. Primary completion30 Sep 2025
  4. Study completion21 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A35-009 (ORION) is a blinded, randomized, placebo-controlled, two-part Phase 2b/3 study, each part consisting of a 52-week double-blind, placebo-controlled phase followed by an optional 52-week open-label extension phase.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
139 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06122662
Sponsor's protocol ID
A35-009
Acronym
ORION
Status last verified
Apr 2026
First submitted
3 Nov 2023
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing AMX0035 in people with Progressive Supranuclear Palsy and PSP, run by Amylyx Pharmaceuticals Inc. at 62 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 sites in United States, France, Germany, Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06122662.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in