AMX0035 and Progressive Supranuclear Palsy
- Conditions
- Neurodegenerative DiseasesAtypical ParkinsonismPSPProgressive Supranuclear Palsy
- Interventions
- Drug: AMX0035Other: Placebo
- Registration Number
- NCT06122662
- Lead Sponsor
- Amylyx Pharmaceuticals Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 110
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AMX0035 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 Placebo Placebo Placebo administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study
- Primary Outcome Measures
Name Time Method Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score 52 weeks 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
- Secondary Outcome Measures
Name Time Method Change in total (10-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score 52 weeks 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
Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) 52 weeks Safety and tolerability of AMX0035 in participants with PSP
Change in MDS-UPDRS Part II Score 52 weeks 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
Trial Locations
- Locations (62)
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Parkinson's & Movement Disorder Institute
🇺🇸Fountain Valley, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Stanford Movement Disorder Center
🇺🇸Palo Alto, California, United States
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States
UC Health Anschutz Outpatient Pavilion Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
UF Health Dorothy Mangurian Neuroimaging Suite
🇺🇸Gainesville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Parkinsons and Movement Disorder Center at the Queens Medical Center
🇺🇸Honolulu, Hawaii, United States
Northwestern University PD and Movement Disorders Center
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸Kansas City, Kansas, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
Quest Research Institute
🇺🇸Farmington Hills, Michigan, United States
University of Minnesota, CTSI
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Missouri, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
🇺🇸Las Vegas, Nevada, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Veracity Neuroscience, LLC
🇺🇸Memphis, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Kerwin Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Central Texas Neurology Consultants
🇺🇸Round Rock, Texas, United States
University of Utah Movement Disorders Center
🇺🇸Salt Lake City, Utah, United States
Virginia Commonwealth University Department of Neurology
🇺🇸Richmond, Virginia, United States
Hôpital de la Timone
🇫🇷Marseille cedex 05, Bouches-du-Rhône, France
Hopital Caremeau
🇫🇷Nimes Cedex 09, Gard, France
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
🇫🇷Bordeaux cedex, Gironde, France
CHU de Limoges - Hôpital Dupuytren
🇫🇷Limoges, Haute Vienne, France
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes cedex 09, Ille Et Vilaine, France
Hopital Roger Salengro - CHU Lille
🇫🇷Lille Cedex, Nord, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Universitaetsklinikum Duesseldorf AoeR
🇩🇪Ulm, Baden Wuerttemberg, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden Wuerttemberg, Germany
Krankenhaus Agatharied
🇩🇪Hausham, Bayern, Germany
Klinikum der Universität München
🇩🇪Muenchen, Bayern, Germany
Paracelsus-Elena-Klinik Kassel
🇩🇪Kassel, Hessen, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Sachsen, Germany
Asklepios Fachklinikum Stadtroda
🇩🇪Stadtroda, Thueringen, Germany
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Italy
Azienda Ospedale-Università di Padova
🇮🇹Padova, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
🇮🇹Salerno, Italy
Hospital de Cruces
🇪🇸Barakaldo, Bizkaia, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, València, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Seville, Spain
Related News
Amylyx Pharmaceuticals Reports Third Quarter 2024 Financial Results - Morningstar
- Prev
- 1
- Next