AMX0035 and Progressive Supranuclear Palsy (ORION)

April 25, 2024 updated by: Amylyx Pharmaceuticals Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Fountain Valley, California, United States, 92708
        • Recruiting
        • Parkinson's & Movement Disorder Institute
        • Contact:
        • Principal Investigator:
          • Daniel Truong, MD
      • San Francisco, California, United States, 94158
        • Recruiting
        • University of California, San Francisco (UCSF)
        • Contact:
        • Principal Investigator:
          • Julio Rojas-Martinez
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Recruiting
        • Parkinson's Disease And Movement Disorders Center of Boca Raton
        • Principal Investigator:
          • Stuart Isaacson, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Anne-Marie Wills
        • Contact:
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Quest Research Institute
        • Principal Investigator:
          • Aaron Ellenbogen, MD
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38157
    • Texas
      • Dallas, Texas, United States, 75231
        • Recruiting
        • Kerwin Medical Center
        • Principal Investigator:
          • Diana Kerwin
        • Contact:
      • Round Rock, Texas, United States, 78681
        • Recruiting
        • Central Texas Neurology Consultants
        • Contact:
        • Principal Investigator:
          • Elizabeth Peckham, MD
    • Virginia
      • Richmond, Virginia, United States, 23298-0059
        • Recruiting
        • Virginia Commonwealth University Department of Neurology
        • Principal Investigator:
          • Matthew Barrett
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
Time Frame: 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
52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time Frame: 52 weeks
Safety and tolerability of AMX0035 in participants with PSP
52 weeks
Change in total (10-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
Time Frame: 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
52 weeks
Change in MDS-UPDRS Part II Score
Time Frame: 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; Total scores range from 0-52 with lower scores indicating better function
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amylyx Pharmaceuticals Inc.

Investigators

  • Study Director: Study Director, Amylyx Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2023

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

November 3, 2023

First Submitted That Met QC Criteria

November 3, 2023

First Posted (Actual)

November 8, 2023

Study Record Updates

Last Update Posted (Actual)

April 26, 2024

Last Update Submitted That Met QC Criteria

April 25, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A35-009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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