Progressive Supranuclear Palsy, PSP, Neurodegenerative Diseases, Atypical Parkinsonism
Conditions
Keywords
Progressive Supranuclear Palsy, PSP, Steele-Richardson-Olszewski Syndrome, ORION, Amylyx
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.
Interventions
DRUGAMX0035
Proprietary formulation of sodium phenylbutyrate and taurursodiol
OTHERPlacebo
Matching Placebo Comparator
Sponsors
Amylyx Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, Care providers, Investigators, and study staff will be blinded to participant group assignment during the double-blind phase and extension phase
Intervention model description
A35-009 (ORION) is a blinded, randomized, placebo-controlled, two-part Phase 2b/3 study, each part consisting of a 52-week double-blind, placebo-controlled phase followed by an optional 52-week open-label extension phase.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | 52 weeks | Safety and tolerability of AMX0035 in participants with PSP |
Countries
France, Germany, Italy, Spain, United States
Outcome results
None listed