← Trials/Trial dossier/NCT06122662

ORION

CompletedPhase 2 / PHASE3

AMX0035 and Progressive Supranuclear Palsy

A Phase 2b/3 Study of the Safety and Efficacy of AMX0035 in Progressive Supranuclear Palsy (ORION)

Lead sponsor

Amylyx Pharmaceuticals Inc.

Asset

AMX0035

Listed sites

Recruiting sites

Enrollment

139

actual

Study population

Frontotemporal dementia

Key I/E criteria

•MMSE 24•Study partner/caregiver required

Primary endpoint

•Total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDA35-009

NCT IDNCT06122662

Timeline

Milestones

Study first posted2023-11-08actual

Study start2023-12-21actual

Primary completion2025-09-30actual

Study completion2025-10-21actual

Last update posted2026-04-30actual

Assets

Drug assets

AMX0035

Study populations

Who this study enrolls

Frontotemporal dementia

Eligibility

Who can enroll

Minimum age40 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

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)

Endpoints (4)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Disease progression

Function / daily living

Safety / tolerability / PK

Function / daily living

1 endpoint

Secondary/protocol endpoint

Change in MDS-UPDRS Part II Score

Time frame:52 weeks

change from baseline, improvement

Disease progression

2 endpoints

Primary/protocol endpoint

Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score

Time frame:52 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in total (10-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score

Time frame:52 weeks

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Time frame:52 weeks

event count, event

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.