ORION Trial Overview
The Phase 3 ORION trial (NCT06122662) will evaluate if the investigational drug, sodium phenylbutyrate and taurursodiol (ursodoxicoltaurine), also known as AMX0035, is safe and effective as a treatment for adults living with progressive supranuclear palsy (PSP).
AMX0035 is not currently approved by any regulatory agency for the use in PSP.
The trial will compare the safety and effectiveness of AMX0035 to placebo. A placebo looks and tastes the same as the investigational drug and is given the same way. However, the placebo does not contain the investigational drug.
Timeline of the ORION trial
Randomized phase
Participants will be chosen at random to receive AMX0035 or placebo.
Learn About the Study Drug
Open Label Extension (OLE) phase
Participants who complete the randomized phase will be given the option to enroll in the OLE phase where all participants receive AMX0035.
ORION is a double-blind trial which means that during the randomized phase, neither investigators nor participants will know who receives the placebo and who receives AMX0035.
What will the trial measure?
The ORION trial will compare AMX0035 and placebo groups across several measures that are important when treating PSP.
- Safety and Tolerability
- Progression of PSP
- Quality of Life
- Burden of Disease for Both Participants and Caregivers
- Biomarkers
- Survival
Participation in the ORION trial requires a trial partner. A trial partner is someone who regularly provides necessary care for the person living with PSP in the trial and can be a relative, friend, or employed professional.
What to expect if you are eligible to participate in the ORION trial
62 Weeks
Including screening period and follow-up after the treatment period, participants will be in the randomized phase of the ORION trial for a maximum of ~14 months (~62 weeks).
60/40
Participants will have a 60% chance of receiving AMX0035 and 40% chance of receiving a placebo in the randomized phase.
Study Visits
The ORION trial is telemedicine-friendly; after screening and initial visits participants will visit the study clinic every 3 months (up to 7 times) and have regular virtual visits with the study team.
Expect to undergo a brain MRI and lumbar puncture twice during the randomized phase.
Expect to undergo a brain MRI and lumbar puncture 1 additional time during the OLE phase.
Accessibility
Participants will receive the study drug or placebo at the study clinic visits.
Participants and their trial partner can receive travel reimbursement for required in-clinic study visits.
Other Medications
If participants are taking medications such as coenzyme Q10, levodopa/carbidopa, a dopamine agonist, etc., then the dosing of these medications must be stable.
Participants should notify the study doctor of any use of other medicines, including vitamins, nutritional supplements, homeopathic remedies, or over-the-counter medicines.
OLE Phase
Participants completing the double-blind randomized phase can enroll in the Open Label Extension (OLE) Phase. During the OLE phase, all participants receive the investigational drug (no one receives placebo during the OLE).
Please note: if the investigational drug becomes commercially available in a country during the OLE Phase, the OLE Phase may be discontinued in that country.
Questionnaires and Other Documentation
Participants will complete questionnaires at regular intervals throughout the trial.
Participants (with the help of their study doctor or study coordinator) will document all the medications they take, medical aids they use, and falls they experience during the trial.
What to expect if you are a trial partner
The trial partner will need to have frequent contact with the participant (≥10 hours/week) and will accompany the participant to study visits. The trial partner will also complete questionnaires at regular intervals throughout the trial.
What is the investigational drug?1,2
Investigational drug AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (also called ursodoxicoltaurine or TURSO). This combination is also known as PB and TURSO.
How is the investigational drug/placebo administered to trial participants?
The investigational drug or placebo is powder that comes in a packet (also called a sachet). Participants will mix the powder with water and take it by mouth. The placebo will be administered in the same way.
What is required to participate?
Clinical trials have specific eligibility criteria to ensure study goals are met.
Key select eligibility criteria for ORION trial participation include:
- Diagnosis of possible or probable PSP also known as PSP-Richardson Syndrome (based on MDS 2017 criteria)
- Experiencing PSP symptoms for less than 5 years
- Age 40-80 years
- Able to walk independently at least 5 steps with minimal assistance
- Live at home or in an assisted living facility, not in a skilled nursing or memory care facility
- Have a reliable study partner to accompany on study visits
- Willing/able to undergo a brain MRI and lumbar puncture twice during the randomized phase, and 1 additional time during the OLE phase
- Participants must NOT require the use of a feeding tube
If participants are taking medications such as coenzyme Q10, levodopa/carbidopa, a dopamine agonist, etc., then the dosing of these medications must be stable.
Visit www.clinicaltrials.gov for the full ORION trial eligibility criteria.
Where will the ORION trial take place?
The ORION trial will be conducted at numerous centers in North America, Europe, and Japan. The latest information is available at clinicaltrials.gov.
Click on the map below to see clinical site locations. If you are interested in participating in the ORION trial or other clinical trials for PSP, or wish to learn more about possible trial participation, speak with your doctor. Amylyx is unable to provide medical advice or additional trial details beyond what is included in this website.
Sites open for enrollment
Future planned sites
References
- Paganoni S, et al. N Engl J Med. 2020;383:919-930.
- Paganoni S, et al. Muscle Nerve. 2021;63:31-39.doi:10.1002/mus.27091.