ORION: AMX0035 and Progressive Supranuclear Palsy

Sponsor

Amylyx Pharmaceuticals Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06122662

Collaborator

(none)

600

Enrollment

Arms

42.5

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Progressive Supranuclear Palsy PSP Neurodegenerative Diseases Atypical Parkinsonism	Drug: AMX0035 Other: Placebo	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A 52-week double-blind, placebo-controlled phase followed by an optional 52-week open-label extension phaseA 52-week double-blind, placebo-controlled phase followed by an optional 52-week open-label extension phase

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 15, 2023

Anticipated Primary Completion Date :

May 31, 2026

Anticipated Study Completion Date :

May 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 administered by mouth: twice daily for an additional 52 weeks	Drug: AMX0035 Proprietary formulation of sodium phenylbutyrate and taurursodiol
Placebo Comparator: Placebo Placebo administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study	Other: Placebo Matching Placebo Comparator

Arm

Intervention/Treatment

Experimental: 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 administered by mouth: twice daily for an additional 52 weeks

Drug: AMX0035

Proprietary formulation of sodium phenylbutyrate and taurursodiol

Placebo Comparator: Placebo

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

Other: Placebo

Matching Placebo Comparator

Outcome Measures

Primary Outcome Measures

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)

Secondary Outcome Measures

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)
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 (MDS-PDRS) Scale Part II
Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [52 weeks]
Safety and tolerability of AMX0035 in participants with PSP

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)