AMX0035 and Progressive Supranuclear Palsy

NCT ID: NCT06122662

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-21

Study Completion Date

2029-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Progressive Supranuclear Palsy PSP Neurodegenerative Diseases Atypical Parkinsonism

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Participants, Care providers, Investigators, and study staff will be blinded to participant group assignment during the double-blind phase and extension phase

Study Groups

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AMX0035

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 Type EXPERIMENTAL

AMX0035

Intervention Type DRUG

Proprietary formulation of sodium phenylbutyrate and taurursodiol

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching Placebo Comparator

Interventions

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AMX0035

Proprietary formulation of sodium phenylbutyrate and taurursodiol

Intervention Type DRUG

Placebo

Matching Placebo Comparator

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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)
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amylyx Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Amylyx Pharmaceuticals

Locations

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Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Parkinson's & Movement Disorder Institute

Fountain Valley, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Stanford Movement Disorder Center

Palo Alto, California, United States

Site Status

University of California, San Francisco (UCSF)

San Francisco, California, United States

Site Status

UC Health Anschutz Outpatient Pavilion Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Site Status

UF Health Dorothy Mangurian Neuroimaging Suite

Gainesville, Florida, United States

Site Status

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Parkinsons and Movement Disorder Center at the Queens Medical Center

Honolulu, Hawaii, United States

Site Status

Northwestern University PD and Movement Disorders Center

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Site Status

University of Kentucky Medical Center

Lexington, Kentucky, United States

Site Status

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status

Quest Research Institute

Farmington Hills, Michigan, United States

Site Status

University of Minnesota, CTSI

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - Rochester

Rochester, Missouri, United States

Site Status

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Site Status

Veracity Neuroscience, LLC

Memphis, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Kerwin Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Central Texas Neurology Consultants

Round Rock, Texas, United States

Site Status

University of Utah Movement Disorders Center

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University Department of Neurology

Richmond, Virginia, United States

Site Status

Hôpital de la Timone

Marseille, Bouches-du-Rhône, France

Site Status

Hopital Caremeau

Nîmes, Gard, France

Site Status

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, Gironde, France

Site Status

CHU de Limoges - Hôpital Dupuytren

Limoges, Haute Vienne, France

Site Status

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, France

Site Status

Hopital Roger Salengro - CHU Lille

Lille, Nord, France

Site Status

Groupe Hospitalier Pitie-Salpetriere

Paris, , France

Site Status

Universitaetsklinikum Duesseldorf AoeR

Ulm, Baden-Wurttemberg, Germany

Site Status

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status

Krankenhaus Agatharied

Hausham, Bavaria, Germany

Site Status

Klinikum der Universität München

Munich, Bavaria, Germany

Site Status

Paracelsus-Elena-Klinik Kassel

Kassel, Hesse, Germany

Site Status

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, Germany

Site Status

Asklepios Fachklinikum Stadtroda

Stadtroda, Thuringia, Germany

Site Status

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status

Azienda Ospedale-Università di Padova

Padua, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status

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

Roma, , Italy

Site Status

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

Salerno, , Italy

Site Status

Hospital de Cruces

Barakaldo, Bizkaia, Spain

Site Status

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, València, Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario de La Princesa

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Countries

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United States France Germany Italy Spain

Other Identifiers

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A35-009

Identifier Type: -

Identifier Source: org_study_id