AMX0035 and Progressive Supranuclear Palsy (ORION)

Amylyx Pharmaceuticals

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: PSP; Neurodegenerative Diseases; Progressive Supranuclear Palsy; Atypical Parkinsonism

Treatments: Other: Placebo; Drug: AMX0035

Study type: Interventional

Funder types: Industry

Identifiers

NCT06122662

A35-009

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 estimated patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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110 participants in 2 patient groups, including a placebo group

AMX0035

Experimental group

Description:

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

Treatment:

Drug: AMX0035

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo