Clinical trial NCT06122662: AMX0035 and Progressive Supranuclear Palsy
Official title: A Phase 2b/3 Study of the Safety and Efficacy of AMX0035 in Progressive Supranuclear Palsy (ORION)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Progressive Supranuclear Palsy
PSP
Neurodegenerative Diseases
Atypical Parkinsonism
Keywords: Progressive Supranuclear Palsy
PSP
Steele-Richardson-Olszewski Syndrome
ORION
Amylyx
Lead sponsor: Amylyx Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-08
Enrollment: 110
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
timeFrame: 52 weeks
Secondary outcomes:
measure: Change in total (10-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
timeFrame: 52 weeks
measure: Change in MDS-UPDRS Part II Score
timeFrame: 52 weeks
measure: Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Fountain Valley
country: United States
facility: Parkinson's & Movement Disorder Institute
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Movement Disorder Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: Aurora
country: United States
facility: UC Health Anschutz Outpatient Pavilion Anschutz Medical Campus
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: UF Health Dorothy Mangurian Neuroimaging Suite
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Honolulu
country: United States
facility: Parkinsons and Movement Disorder Center at the Queens Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University PD and Movement Disorders Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota, CTSI
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Memphis
country: United States
facility: Veracity Neuroscience, LLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Kerwin Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Movement Disorders Center
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University Department of Neurology
state: Virginia
city: Marseille cedex 05
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Nimes Cedex 09
country: France
facility: Hopital Caremeau
state: Gard
city: Bordeaux cedex
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital Pellegrin
state: Gironde
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
state: Haute Vienne
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
state: Ille Et Vilaine
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Ulm
country: Germany
facility: Universitaetsklinikum Duesseldorf AoeR
state: Baden Wuerttemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Hausham
country: Germany
facility: Krankenhaus Agatharied
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik Kassel
state: Hessen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
state: Sachsen
city: Stadtroda
country: Germany
facility: Asklepios Fachklinikum Stadtroda
state: Thueringen
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Padova
country: Italy
facility: Azienda Ospedale-Università di Padova
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Bizkaia
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: València
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Amylyx Pharmaceuticals
name: Study Director
role: STUDY_DIRECTOR
References: