AMX0035 and Progressive Supranuclear Palsy

NCT06122662 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: A35-009
• Study Type: interventional
• Target: 139
• Locations: 5 countries
• Sites: 62

Brief 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.

Conditions

Progressive Supranuclear Palsy; PSP; Neurodegenerative Diseases; Atypical Parkinsonism

Keywords

Progressive Supranuclear Palsy; PSP; Steele-Richardson-Olszewski Syndrome; ORION; Amylyx

Outcome Measures

Primary Outcomes (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

  52 weeks

Secondary Outcomes (3)

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

  52 weeks

• Change in MDS-UPDRS Part II Score

  52 weeks

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

  52 weeks

Study Arms (2)

AMX0035

EXPERIMENTAL

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

Drug: AMX0035

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

AMX0035 DRUG

Proprietary formulation of sodium phenylbutyrate and taurursodiol

AMX0035

Placebo OTHER

Matching Placebo Comparator

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead

Study Sites (62)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Parkinson's & Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford Movement Disorder Center

Palo Alto, California, 94304, United States

Location

University of California, San Francisco (UCSF)

San Francisco, California, 94158, United States

Location

UC Health Anschutz Outpatient Pavilion Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

UF Health Dorothy Mangurian Neuroimaging Suite

Gainesville, Florida, 32608, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Parkinsons and Movement Disorder Center at the Queens Medical Center

Honolulu, Hawaii, 96813, United States

Location

Northwestern University PD and Movement Disorders Center

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536-0274, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

University of Minnesota, CTSI

Minneapolis, Minnesota, 55414, United States

Location

Mayo Clinic - Rochester

Rochester, Missouri, 55905, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Veracity Neuroscience, LLC

Memphis, Tennessee, 38157, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Kerwin Medical Center

Dallas, Texas, 75231, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

University of Utah Movement Disorders Center

Salt Lake City, Utah, 84108, United States

Location

Virginia Commonwealth University Department of Neurology

Richmond, Virginia, 23298-0059, United States

Location

Hôpital de la Timone

Marseille, Bouches-du-Rhône, 13385, France

Location

Hopital Caremeau

Nîmes, Gard, 30029, France

Location

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, Gironde, 30076, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, Haute Vienne, 87042, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, 75013, France

Location

Universitaetsklinikum Duesseldorf AoeR

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Krankenhaus Agatharied

Hausham, Bavaria, 83734, Germany

Location

Klinikum der Universität München

Munich, Bavaria, Germany

Location

Paracelsus-Elena-Klinik Kassel

Kassel, Hesse, 34128, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 1307, Germany

Location

Asklepios Fachklinikum Stadtroda

Stadtroda, Thuringia, 7646, Germany

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Azienda Ospedale-Università di Padova

Padova, 35128, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 168, Italy

Location

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

Roma, 185, Italy

Location

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

Salerno, 84131, Italy

Location

Hospital de Cruces

Barakaldo, Bizkaia, 48903, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, València, 46026, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Neurodegenerative Diseases

Interventions

sodium phenylbutyrate and taurursodiol

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Study Director

  Amylyx Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, Care providers, Investigators, and study staff will be blinded to participant group assignment during the double-blind phase and extension phase
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 3, 2023
• First Posted: November 8, 2023
• Study Start: December 21, 2023
• Primary Completion: September 30, 2025
• Study Completion: October 21, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

ES (7); IT (6); US (35); FR (7); DE (7)