AMX0035 and Progressive Supranuclear Palsy

Neurodegenerative Diseases Clinical Trial

— ORION  

Official title:

A Phase 3 Study of Safety and Efficacy of AMX0035 in Progressive Supranuclear Palsy (ORION)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06122662
• Other study ID #: A35-009
• Status: Recruiting
• Phase: Phase 3
• Start date: December 21, 2023
• Est. completion date: May 31, 2027

Study information

• Verified date: April 2024
• Source: Amylyx Pharmaceuticals Inc.
• Contact: The Harte Group
• Phone: +44 (808) 1642604
• Email: clinicaltrials[@]amylyx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

AMX0035 is a 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Atypical Parkinsonism
• Neurodegenerative Diseases
• Paralysis
• Parkinsonian Disorders
• Progressive Supranuclear Palsy
• PSP
• Supranuclear Palsy, Progressive

Intervention

Drug:
• AMX0035
Proprietary formulation of sodium phenylbutyrate and taurursodiol

Other:
• Placebo
Matching Placebo Comparator

Locations

Country	Name	City	State
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Kerwin Medical Center	Dallas	Texas
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Parkinson's & Movement Disorder Institute	Fountain Valley	California
United States	Veracity Neuroscience, LLC	Memphis	Tennessee
United States	Virginia Commonwealth University Department of Neurology	Richmond	Virginia
United States	Central Texas Neurology Consultants	Round Rock	Texas
United States	University of California, San Francisco (UCSF)	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Amylyx Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	52 weeks
Secondary	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 (MDS-PDRS) Scale Part II; Total scores range from 0-52 with lower scores indicating better function	52 weeks
Secondary	Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Safety and tolerability of AMX0035 in participants with PSP	52 weeks